Indepth pharmacology and nutritional properties of Aegle marmelos

1. In-depth pharmacological and nutritional properties of bael (Aegle
marmelos): A critical review
Tanmay Sarkar a,b
, Molla Salauddin a
, Runu Chakraborty a,*
a
Department of Food Technology and Biochemical Engineering, Faculty of Engineering and Technology, Jadavpur University, Jadavpur, Kolkata, 700032, India
b
Malda Polytechnic, West Bengal State Council of Technical Education, Govt. of West Bengal, Malda, 732 102, India
A R T I C L E I N F O
Keywords:
Ethnobotany
Traditional fruit
Food product
Medicinal plant
Pharmacology
A B S T R A C T
Aegle marmelos or bael has been known from prehistoric times in India with mythological importance. Each part of
the tree like root, bark, fruit, leaf, and flower has therapeutic significance in Ayurvedic as well as other traditional
medicinal systems in treating ailments. Modern researches have successfully supported the pharmacological ac-
tion of bael by discovering the presence of valuable bioactive compounds. Studies have revealed the anti-oxidant,
anti-microbial nature of bael which aids in inhibiting gastrointestinal problems, different cardiac issues. Hep-
atoprotective, radioprotective, anti-diabetic, wound healing activities are also unveiled by bael. The aim of the
present research work is to study the ethno-botanical importance of each part of the tree, nutritional and
phytochemical profiling, preservation techniques of the fruit, and medicinal actions of it.
1. Introduction
The subtropical fruit Aegle marmelos or commonly known as Bael
belongs to the Rutaceae family [1]. Though being native to northern
India, widespread cultivation is found in other parts of India as well as in
Thailand, Bangladesh, Pakistan, Sri Lanka, and Burma [2]. In different
languages bael is named differently like Bilva, Shivaphala in Sanskrit,
Belo in Oriya, Bel in Assamese and Marathi, and Vilva marum in Tamil in
India, Be Li in Sinhalese, Matoom in Thai, Bela in Spanish [3]. There are
several plants which have tremendous therapeutic application in Indian
medicine system from ancient time and bael fruit is one of them. It also
possesses great mythological importance in the Hindu religion. Leaf of
this sacred tree which is vernacularly known as Tripatra has been
essential in offerings to Lord Shiva [1]. Every part of this tree such as
root, bark, leaf, flower, and fruit can be utilized in different fields. The
wild variety of fruit is smaller in size than the cultivated type and also not
popular for commercial purposes [1]. A wide range of cultivar variety
includes Kagzi Gonda, Gonda no 1, Gnda no 2, Kagzi Etawah, Mirzapuri,
and Baghel [1]. A different medicinal system like Siddha, Unani and
Ayurvedic systems provide information about the potential effects of bael
[4]. Various studies on bael reveal that it acquires a variety of nutritional
elements like a large group of phytochemicals which includes phenolic
acids, flavonoids, alkaloids, tannins, and coumarins. Other than these,
amino acids, fatty acids, a wide range of organic acids, minerals,
carbohydrates, vitamins, fibers make bael a highly nutritious fruit with
immense health benefits [5]. Gastro-intestinal problems, diseases like
diabetes, cardiac issues, and inflammation-related problems may be
cured with the fruit. Protective effects against the wound, radiation,
microbes, free radical generation, and depression have also been
exhibited by bael. These records prove the natural healing power of bael
[6]. These beneficial effects of bael cannot be used throughout the year as
it is a seasonal fruit and mostly available during May and June therefore
may not be available during the rest of the year [1]. Hence these prob-
lems inspire in making different products with the fruit. Juice, different
beverages can be made with it. Dehydrated bael products include jam,
slab, bael powder. Wine and tea can also be prepared with it. Thus from
an economical point of view making various products with bael is
extremely profitable. Till date, various researchers have discussed the
botany of the tree [1], the nutritional composition of fruit [1], quantifi-
cation of phytochemicals [7], different health benefits of the fruit [6],
products made out of the fruit [8] but all those studies mainly concen-
trate on either topic mentioned while in gathering knowledge about the
fruit it is highly recommended to thoroughly discuss the fruit in all
perspective. Taking care of this matter the study has concentrated
different findings related to bael in a composite manner.
Thus the objective of the present study concerns in the field of the
botanical description of bael, traditional uses, nutritional as well as
phytoconstituent formulation, quantification of phytochemicals, a brief
* Corresponding author.
E-mail address: crunu@hotmail.com (R. Chakraborty).
Contents lists available at ScienceDirect
Journal of Agriculture and Food Research
journal homepage: www.journals.elsevier.com/journal-of-agriculture-and-food-research/
https://doi.org/10.1016/j.jafr.2020.100081
Received 11 October 2020; Received in revised form 19 October 2020; Accepted 19 October 2020
2666-1543/© 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Journal of Agriculture and Food Research 2 (2020) 100081

2. description of products made out of it and emphasizes on a vast appli-
cation in the medicinal area.
2. Botanical description
This slow-growing tree is found to have a medium height of nearly
about 762 cm and plant parts include bark, leaf, flower, fruit, and seed.
Spiny branches of steam are observed in the bael tree [9]. The leaves are
in an alternate fashion, generally trifoliate, contains leaflets of 3–5
numbers, having a length of 4–10 cm, with 2–5 cm width. A compara-
tively lighter green colour is seen among young leaves, whereas it be-
comes dark green on maturation [9]. The bark of the tree is thick and
flaking, often spiny branches. From the wounded bark a gum secretion is
observed, which turns thick when comes in contact with air [9]. The
flower of bael is of a greenish-white colour. Having a sweet scent, it also
characterizes as having bisexual, ebracteate, hypogynous, actinomorphic
stalk. The leaf axil holds some lateral panicles which contain ten flowers
[1,10]. The bael fruit colour is mainly yellowish green, having a diameter
of 5.3–7.2 cm, with an approximate weight of 77.2 g, volume of 73.7 mL,
and sphericity of 93.72 2.78% [11]. The pulp of the fruit is yellow in
colour and mucilaginous. It contains some dots on the outer surface and
also contains numerous seeds, which are hard and having a thread like
hairs over their outer surface which is white [10,11].
3. Traditional uses
Extensive use of bael has been found in Ayurveda and traditional
medicine system. Each part bael tree is found to have the potential for
curing various diseases [10].
3.1. Leaf
In the treatment of jaundice, asthma, it is found to be very useful [9].
Bael leaves are a good aid in removing mucilage secretion from bronchial
tubes. Application is found in conjunctivitis treatment and even in curing
constipation, deafness, and leucorrhoea. Bowel syndrome may be treated
by bael leaf powder [12]. It is used as a remedial measure in the treat-
ment of beriberi [13]. Bael leaf essential oil is reported to show various
therapeutic actions [14].
3.2. Fruits
Treatment of thyroid in body parts has been accelerated with fruit
extract. It is thought to be very helpful in curing vomiting during preg-
nancy when taken with rice water in boiling conditions. In abscess
curing, pulp powder of unripe fruit is very helpful [15]. Starch present in
unripe fruit converts to sugar with heat treatment, then the fruit extract is
added with hot water and anesi and strained, the extract found is useful
in dysentery. Fruit pulp in milk mixed with sugar is helpful in urino-
genital disorders [8,13]. It may be used as an antiscorbutic and stomatic
agent. Intestinal ulcer as well as chronic constipation and indigestion
related issues may be cured [13]. It may also be used in gonorrhea, heart
tonic, and epilepsy. Ripe fruit juice extract helps in lowering blood sugar
levels owing to its bitter flavour. Chronic gastrointestinal disorder, piles
treatment, and rectum inflammation have also been found to get cured
[16,17]. Faecal matter accumulated for long days can get cleared from
the bowel with 2–3 months of consumption of bael in the form of sherbet
[1,9]. Powdered fruit and mustard oil in the ratio 1:2 is used in southern
Chattisgarh in burn treatment [1].
3.3. Flower
The flower has astringent as well as antiseptic properties, used in
epilepsy [19]. Marmala water, isolated after distillation from the flower
is found helpful in catering conjunctivitis [18]. Bael flower extract has
been tested for wound healing properties [19]. It is reported that mRNA
expression has been increased by inhibition of nitric oxide, the release of
prostaglandin E2 (PGE2), thus increasing wound healing in rats [20].
3.4. Root and bark
The decoction of root and bark is useful in melancholia, heart palpi-
tation, and intermittent fever. In preparation for a popular ayurvedic
medicine dashmula bael tree root is used as one of the ingredients. Bael
root extract with onion, turmeric in equal proportion has been useful in
secretion from ears (Kala 2006). It is used as one of the ingredients of
Chyavanprash [15]. Root bark may be used as a fish poison and fever
treatment [21], whereas bark decoction, leaf extract with honey and bael
extract is used in fever, febrifuge as well as in intermittent fever [22–24].
4. Nutritional composition
It is evident from various studies over the nutritional composition of
bael, the fruit is rich in various nutrients which are extremely beneficial
for human health. Reportedly the fruit contains carbohydrates, different
vitamins, a good number of minerals, various fatty acids, and amino
acids. It is highly rich in fiber, glucose, and sugar [4,25,26]. Being highly
rich in vitamins like vitamin A, vitamin B group, and vitamin C bael is
found to act as an antioxidant, thus preventing rancidity and colour loss
[4]. From the edible portion of fruit, the available minerals reported are
iron, calcium, potassium, phosphorus, and their salts [27,28]. Methods
used in estimating crude protein content in dried fruit pulp are micro
Kjeldahl's distillation, crude fat in the soxhlet method, ash content by
incineration [13,29]. Sampathkumar et al., 2012 have identified the
unripe fruit are more advantageous in medicinal purposes over the ripe
fruit. It contains moisture (61.0%), mineral (1.9%), phosphorus (52 mg),
potassium (610 mg), calcium (80 mg), fiber (2.9%), protein (1.6%) and
carotene (55 mg) in fruit juice [8,30]. Standard AOAC (Association of
Official Agricultural Chemists) [30] method has been employed in esti-
mating protein, moisture, fat, and ash content. The total carbohydrate
has been determined by the difference method. It has been found that
bael leaves contain higher moisture content (71.26%) than that of fruit
(63.04%) and seed (53.75%). Bael seed possesses a higher amount of fat
content (14.94%). Fruit pulp and the leaves are very low in the fat con-
tent of 0.28% and 0.07% respectively [31]. Other studies have also found
bael contains alpha-curcumin (9.56%), alpha-zingiberene (14.41%),
mycrene (1.22%), beta-sesquiphellandrene (12.85%), ethanone, 1,
2-dicyclopropyl- (0.90%), 1,7-nonadiene, 4,8-dimethyl-1-nitro-, (e)-
(2.25%), citronellyl propionate (4.39%), nonanoic acid, methyl ester
(2.23%), phytol (50.88%) and 4,8-dimethyl-3(e),7- nonadienyl thio-
acetate (1.39%) [7,16,27]. A study on bael essential oil depicts that there
is seasonal variation in yield and composition of essential oils [32]. A
dimeric protein, novel lectin is found in bael which specifically binds
with sialic acid, mannose, and N-acetylgalactosamine [3,33]. The nutri-
tional composition of bael reported by different researchers has been
displayed in Table 1.
5. Phytochemicals in bael
Bael contains a good number of polyphenols as well as flavonoids.
Bael fruit pulp, fruit juice have been reported to be rich in numerous
health-boosting polyphenols. Alkaloids, flavonoids, phenolic com-
pounds, terpenoids have been accumulated in bael pulp. The most
important polyphenols and flavonoids include alkaloids, coumarins,
polysaccharides, and carotenoids. Polyphenols present in bael depends
on the maturity stage of bael [34]. From showing anti-oxidant activities
to lipid cholesterol absorption these phytochemicals possess immense
health benefits. Phenolic compounds in bael fruit juice include caffeic
acid, arbutin, cholorogenic acid, p-coumaric acid, p-coumaroyl, quinic
acid, and protocatecheuic acid [4]. Terpenoids, flavonoids, saponins,
tannins, glycosides have been isolated from bael fruit [7]. Bael leaves also
retains phytochemicals in a good amount, the reported compounds
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
2

3. include γ-sitosterol, rutin, β-sitosterol, glycosides, marmeline, aegelin,
marmesinin, halfordiol, phenyl ethyl cinnamamides and lupeol [35].
Catechin, flavanols, flavones, lignin, tannins, and iso-flavones fall under
the polyphenol group [4]. lignan glucoside compounds have been iso-
lated from the bark of bael tree [36]. 7, 8- dimethoxy-1- hydrox-
yl2-methyl anthraquinone and 6-hydroxy-1-methoxy-3-methyl
anthraquinone have been reported to be isolated from bael [37]. Skim-
miarepin A as well as skimmiarepin C have been isolated from stem bark
[38]. Details of different phytochemicals found in different parts of bael
are represented in Table 2.
6. Bael product
Various bael products have been developed from different parts of the
bael tree. As bael is highly rich in enormous nutrients but being a sea-
sonal fruit utilisation of nutrients may not be available throughout the
year, since it is utmost required to make several bael products to get those
valuable nutrients available. Different bael products developed by re-
searchers are reported in Table 3.
7. Quantitative estimation of phytochemicals
From the nutritional composition of bael, it is well known that the
fruit is highly rich in various phytochemicals. Therefore many studies
have already reported different phytochemical assay (Table 4). Quanti-
tative estimation of different phytochemicals for bael fruit, bark, and
flower has been done by various researchers. Total phenolic content
(TPC) is generally estimated using Folin-ciocalteu assay, in which gallic
acid is taken as a standard for calibration. On the other hand, aluminium
chloride colorimetric assay has been used in determining total flavonoid
content (TFC). In that case, catechin or rutin is used as a standard. It is
evident from the result that phenolic content falls in the range of me-
dicinal plants which shows anti-cancer activity. In comparison to other
medicinal plants, TFC was also found to be higher in bael fruit. Total
carotenoids (TC) have been determined using the Gross method. The
spectrophotometric method is used with absorbance at 470 nm. Ascorbic
acid is quantitatively determined following Pearson's method. Tannin
content is estimated by Folin-Denis reagent with spectroscopic assay at
700 nm. Total alkaloid is quantified by the ammonium hydroxide pre-
cipitation method.
8. Medicinal properties of bael
8.1. Diarrohoea and dysentery
Chronic diarrohoea can be treated with the use of bael fruit especially
half-ripe or unripe fruit. Dried bael fruit powder is the best one for this
purpose. Unripe fruits may be baked and after that, it may be mixed with
jaggery for consumption [39]. The astringency of unripe fruit is the key
to treat chronic diarrohoea and dysentery (Fig. 3). Over 35 strains of
bacteria that cause diarrohoea, Vibrio cholera, Escherichia coli, and Shigella
sp are effectively inhibited by ethanolic extract of fruit [6,40]. After
consuming fruit powder gradually stool becomes solid and blood, mu-
cous also disappear from stool [13]. S. sonnei, Shigella boydii, S. flexneri
are strongly inhibited by ethanolic extract whereas moderate activity is
exhibited against S. dysenteriae. There are various studies on in vitro and
in vivo antidiarrhoeal properties of bael fruit. One of them is done by
Mazumder et al., 2006 [40] where the in vitro studies show chloroform
extract of bael root can be as effective as ciprofloxacin [41]. The unripe
fruit pulp has potential activity against enterotoxins. It can also prevent
colony formation from gut epithelium [41]. Bael juice, water extract of
unripe fruit, dried fruit pulp, and bael leaf possess anti-diarrhoeal activity
[42–45]. Anti-diarrhoeal activity is judged by the minimum inhibitory
concentration (MIC) method. Tannin present in bael exhibits astringent
properties, a magical remedy for diarrhoea [46,47]. Ames assay has
shown the non-mutagenic behaviour of bael to Salmonella typhimurium
strain TA 100 [48,49]. When a dosage of 6 g/kg bodyweight of bael
extract is applied to mice it shows a non-toxic effect [49,50]. In exper-
imenting with any adverse effect of bael it has been noticed that no such
effect has been seen for 30 days for a maximum of 250 mg/kg body-
weight administration [51–53]. Anti giardial effect is exhibited by the
decoction of unripe fruit [49]. Colonization of different organisms like
Table 1
The nutritional composition of bael (Aegle marmelos).
Components [215] [216] [5] [8] [13] [217] [218] [219] [219]
Energy(Kcal) - 138 139 142 135 137 130 129 137
Potassium(mg) 603 - 585 610 600 590 600 600 600
Phosphorus(mg) 51.60 - 50 52 50 50 50 50 50
Iron(mg) 0.55 - 0.6 0.5 0.8 0.6 0.3 0.3 0.5
Calcium(mg) 78.0 - 85.0 80.0 85.0 85.0 60.0 90.0 85.0
Vitamin C(mg) - - 8.0 8.0 8.6 8.0 10.0 10.0 8.0
Vitamin B3(mg) - - 1.1 1.1 1.0 0.87 0.9 0.90 0.89
Vitamin B2(mg) - - 1200 1000 1190 - 1200 1200 -
Vitamin B1(mg) - - 13.0 12 11.9 9.0 10.0 10.0 9.0
Vitamin A(μg) - - 55 55 56 55 - 186 -
Fibre (%) 4.80 2.78 2.9 2.9 2.8 3.0 2.2 2.2 2.9
Fat (%) 0.43 0.28 0.3 0.2 0.3 0.3 0.2 0.2 0.3
Protein (%) 3.64 1.87 1.8 1.6 1.8 1.8 1.8 1.8 1.8
Carbohydrate (%) – 34.35 31.8 30.5 31.8 31.8 31.8 30.6 31.8
Moisture (%) 61.06 63.04 61.5 61.0 62.5 61.0 64.2 64.2 61.5
Energy(Kcal) - 138 139 142 135 137 130 129 137
Potassium(mg) 603 - 585 610 600 590 600 600 600
Phosphorus(mg) 51.60 - 50 52 50 50 50 50 50
Iron(mg) 0.55 - 0.6 0.5 0.8 0.6 0.3 0.3 0.5
Calcium(mg) 78.0 - 85.0 80.0 85.0 85.0 60.0 90.0 85.0
Vitamin C(mg) - - 8.0 8.0 8.6 8.0 10.0 10.0 8.0
Vitamin B3(mg) - - 1.1 1.1 1.0 0.87 0.9 0.90 0.89
Vitamin B2(mg) - - 1200 1000 1190 - 1200 1200 -
Vitamin B1(mg) - - 13.0 12 11.9 9.0 10.0 10.0 9.0
Vitamin A(μg) - - 55 55 56 55 - 186 -
Fibre (%) 4.80 2.78 2.9 2.9 2.8 3.0 2.2 2.2 2.9
Fat (%) 0.43 0.28 0.3 0.2 0.3 0.3 0.2 0.2 0.3
Protein (%) 3.64 1.87 1.8 1.6 1.8 1.8 1.8 1.8 1.8
Carbohydrate (%) – 34.35 31.8 30.5 31.8 31.8 31.8 30.6 31.8
Moisture (%) 61.06 63.04 61.5 61.0 62.5 61.0 64.2 64.2 61.5
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
3

4. S. flexneri, E. coli B170, E. coli E 134 is studied. Bacterial entry may be
prevented with modification in cell receptors or may be due to metabo-
lization of Hep-2, thus colonization is reduced in this way. E. coli E134
and S. flexneri are more likely to be inhibited by bael decoction than
E. coli B170 [49]. Bacterial metabolism may be affected by decoction, this
may be supported by the fact that LT (E. coli heat-labile toxin), as well as
CT (cholera toxin) bonding with GM1 (Ganglislioside monosialic acid), is
retarded. They may form bonding with common antigenic moiety present
in this toxin or by blocking directly GM1 consequently inhibits the
binding receptor. Also, it may be noted that CT production is reduced
[49]. In albino rats, which is an experimental model with inflammatory
bowel disease (IBD) the unripe fruit extract is appeared to be effective. A
reduction of intestinal inflammation with unripe fruit extract is the
outcome of this experiment. Interleukin (IL1, IL6, and IL8), tumor ne-
crosis factor (TNF)-α these inflammatory mediators are inhibited as a
result of which the effect of unripe fruit extract is seen [54]. Intestinal
mortality, secretion is retarded by the anti-diarrhoeal property of unripe
fruit extract [55].
8.2. Diabetes
Diabetes is known to occur in the human body due to lack of insulin,
so in the treatment of diabetes it is required to get insulin externally, in
similar fashion bael can replace insulin by enhancing the external glucose
uptake ability [1]. A study of Upadhya et al., 2004 reveals the hypogly-
cemic effect has been exhibited by aqueous extract of bael leaves which is
supported by the analysis based on plasma urea, glutathione-S-transfer-
ase, and glucose, as well as malondialdehyde ( MDA) and glutathione
(GSH) levels, checked for erythrocytes in alloxan-induced diabetic rat
[56]. Another report by Sachdewa et al., 2001 where they have experi-
mented on hyperglycemic rats about the hypoglycemic effect of bael
[57]. Hema et al., 1999 have experimented with three different extracts
namely petroleum ether, aqueous and alcoholic extract of bael to see the
hypoglycemic effect [58]. A dose of 500 mg/kg of bael aqueous and
alcoholic extract shows the said effect on fasted rats. Fruit juice can lower
clotting which in a way affects the blood circulation thus improving
diabetic condition. In an experiment with diabetic animal, it is observed
Table 2
Phytochemical constituents found in different parts of Bael, their availability, method of detection, and activities.
Name of
Phytochemical
Occurrence in
part of Bael Tree
Examples Identifying Test Activities References
Alkaloids fruits and leaves marmeline, halfordino, ethyl cinnamamide, aegelinosides
A, aegelinosides B, O-3, 3-(di-methylallyl) halfordinol,
ethyl cinnamate, N-2-ethoxy-2-ethyl-cinnamid, N-2-
methoxy-2-[4-(3',3'-dimethylallyloxy) phenyl] ethyl
cinnamate, aegelin, dictamine, aegelenine, fragrine, O-
methylhalfordinine, N-4-methoxystyryl cinnamide, O-
isopentenyl halfordinol, and N-2-ethoxy-2-(4-methoxy
phenyl) ethyl cinnamide, N-2-hydroxy-2-(4-
hydroxyphenyl) ethyl cinnamide, marmelosin, marmin,
3marmesin, and rutacine
Dragendorff’s test, Hager’s
test, Mayer’s test,
Wagner’s test
alpha-glucosidase inhibitor,
anti-inflammatory, anti-
bacterial, analgesic effects
[27,220–224]
Coumarins fruit, seed,
leaves, bark,
root
marmelosin, marmenol (7-geranyloxycoumarin [7-(2,6-
dihydroxy-7-methoxy-7-methyl-3-octaenyloxy) coumarin]
marmin, methyl ether, scoparome, imperatorin,
umbelliferone, marmelide, scopolentin, [7-(2,6-dihydroxy-
7-methoxy-7-methyl-3-octaenyloxy) coumarin], psoralen,
alloimperatorin, zanthotoxol, 6', 7’–epoxyauraptene
Permanganate oxidation
method, Colorimetric
method
anti-inflammatory, anti-
oxidant, anti-diabetic,
analgesic agents
[1,190,
223–228]
Terpenoid fruit, leaf, and
bark
α-phellandrene, p-cymene, p-Menth-1-en-3, 5-diol,
Limonene, β-myrcene, α-pinene, δ-carene, β-ocimene,
isosylvestrone, linalool, terpenolene, γ-terpinene, 3-iso-
thujanol, thug-3-en-10-al, δ-elemene, 4-terpineol,
α-cubebene, γ-elemene, α-humulene, γ-muurolene,
γ-curcumene, valencene, β-selinene, β-bisabolene,
β-bisabolol, γ-cadinene, α-terpinyl isobutyrate, 2E, 6E)-
Farnesal, (2E,6E)-Farnesol, (3Z)-Hexanylbutanoate, (3Z)-
Hexanol, hexanylhexanoate, methyl perilate, α-Cardinol,
cineol, α-Cedrene, cis-Limonene oxide, α-Copaene, cis-
Linalool oxide, elemol, α-Zingiberene, epi-Cubebal,
limonene (a relatively stable terpene) (67.83%),
caryophyllene (8.76%), α-Ocimene (4.84%), cubedol
(3.29%), humulene (2.84%), myrcene (2.60%), α-Copaene
(2.53%)
Noller’s test, antimalarial and anti-cancer
drug
[10,27,153,
220,
228–231]
Phenolic acids Fruit chlorogenic acid (136.8 μg/g), rutaretin, gallic acid
(873.6 μg/g), egallic acid (248.5 μg/g), ferulic acid
(98.3 μg/g), procatechuic acid (47.9 μg/g), syringic acid,
gentisic acid, caffeic acid, vanillic acid and p- coumaric
acid
ferric chloride test, LC-MS
and HPLC (full form)
studies
antioxidant activity [231,232]
Flavonoids quercetin (56.9 μg/g), rutin, catechin, flavan-3-Ol,
flavonoid glycosides,
Shinoda’s test Antioxidant activity [27,231,233]
Caroetnoids fruit HPLC method Antioxidant activity [5]
Tannins unripe stage of
bael fruit
4, 7, 8-trimethoxyfuro-quinoline, skimminianine, Gelatin Test, Goldbeater’s
Test
antimicrobial properties,
helps in reducing blood
pressure, serum lipid levels
[48,215,234,
235]
Amino acids Fruit, Bark phenyl alanine, tyrosine, and leucine, methionine and
isoleucine, aspartic acid, arginine, alanine,
Ninhydrin Test, Millon’s
Test
helps in improving insulin
sensitivity
[7,205,228,
236]
Organic acid fruit oxalic acid, 0.155% for malic acid, 0.215% for tartaric
acid,
HPLC method Antimocrobial activity [235,237]
Fatty acid seed, fruit, leaf linoleic, palmitic, stearic, linolenic acid, oleic acid, linoleic
acid, oleic acid, Ricinoleic acid, stearic and linolenic acid,
Tetradecanoic acid or myristic acid, Pentadecanoic acid,
Stearic acid, palmitoleic acid,
Gas chromatography with
a flame ionization detector
antimicrobial activity [16,228,231,
238,239]
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
4

5. that up taking of fruit juice can help in lowering oxidative stress, due to
falling in lipid peroxidation, hydroperoxide level, and conjugated diene
while increase in glutathione level, catalase, superoxide dismutase level
in serum, and liver [59]. Amino acid and dietary fiber present in bael aid
in sugar absorption moderately [5]. It is found to be better than the
antidiabetic drug, glibenclamide when taken at a dosage of 250 mg/kg
[53]. Kamalakkannan and prince, 2003 [53] have reported that
coumarin present in bael may be the key which promotes the secretion of
Table 3
Utilisation of different portions of bael (Aegle marmelos) in food and/or feed application. Where, RTS ¼ ready to serve, RSM ¼ response surface methodology,
ANN ¼ artificial neural network, KMS ¼ Potassium metabisulfite, DPPH ¼ 2, 2-diphenyl-1-picrylhydrazyl, ABTS ¼ 2, 2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic
acid, H2O2 ¼ Hydrogen peroxide.
Part of tree Product name Method of Preparation Aim of Study Key feature Reference
Bael fruit
pulp
Fruit Juice Juice extraction utilizing enzymes Juice recovery by pectinase and cellulose
enzyme
82.9% juice recovered at 45
C for 475 min
incubation.
[240]
Fruit beverage Juice extraction and fortified with
whey protein and pectin, carboxy
methyl cellulose
Protein enrichment in beverage Optimised product found with 3.75% whey
protein -carboxymethylcellulose and 25% bael
pulp
[154]
RTS beverage Juice extraction and mixed with
guava juice
Storage study over 2 months at 30–35
C Browning, acidity and sugar increased;
Vitamin C, pH, phenolics content decreased.
[241]
Jam Bael and apple pulp Functional food development Ascorbic acid and phenolics decreased [242]
Therapeutic
beverage
Formulation and Storage study Best squash: 35% pulp with 1.2% acidity and
35% total solid
[32]
Fruit juice Water extraction Preservation of juice Preservation was achieved by 30 min
pasteurisation at 80
C
[243]
RTS beverage Bael juice extraction and mixed
with Jalgerra and tarmarind juice
New product development and
preservation
Jalgerra and blended juice with 1:9 ratio was
found best.
[243]
RTS beverage Bael juice extraction and mixed
with citrus fruit (lime, sweet
orange and pineapple)
Storage stability and quality analysis Blended juice can be preserved up to two
months.
[244]
Bael wine Yeast fermentation preservation Wine production Optimum production condition: 88 h, pH
5.5 at 25
C
[151]
Bael candy Preservation with sugar syrup New product development 8–10 h drying at 55–60
C; storage in
polythene packet.
[240]
Bael candy Preservation with sugar syrup New product development Shelf life: 4 months in polythene pouch. [89]
Bael toffee Preservation with sugar syrup New product development Pulp, butter, milk powder, sugar mixed and
heated at 100–154
C
[240]
Bael slab Drying New product development Pulp with 35% total solid, 0.07% KMS, 0.5%
acidity and sugar dried for 15–16 h at
55–60
C.
[240,
247]
Bael jam Bael pulp and mango pulp are
preserved with sugar
New product development 45%, 1:1 bael and mango pulp; 0.5% acidity. [89]
Bael jam Preservation with sugar New product development 75% sugar, 0.3% citric acid contained jam
stored in glass bottle.
[240]
Bael powder Dehydration and grinding Preservation Should be stored at dry place in polythene bag [240]
Bael powder Dehydration and grinding Moisture adsorption isotherm Peleg model fitted best. Type-II sigmoid
isotherm.
[189]
Green and ripe
bael powder
Dehydration and grinding Fat, protein, carbohydrate and mineral
analysis
Carbohydrate and Iron more in green powder. [245]
Bael powder Freeze drying Preservation Better antioxidant activity after drying. [231]
Bael panjiri Dehydration and grinding New product development Pulp: butter oil: sugar ¼ 1:1:1.5 and roasting [240]
Bael wine Yeast fermentation Moisture, sugar, phenolics, vitamin C,
fat,protein, vitamin, pH, TSS, acidity,
β-carotene, sensory evaluation
7.87% ethanol content.
Antioxidant enriched medicinal wine.
[151]
Bael toffee Preservation with sugar New product development Cardamom, cinnamon, sugar, citric acid
enriched toffee.
[103]
Bael and aloe
vera beverage
Bael and aloevera juice extraction New product development Nutritive product with 15 days of shelf-life. [37]
Bael beverage Juice extraction New product development Jaggery and lime fortified beverage [246]
Bael jam Preservation with sugar New product development Pulp: sugar (1:1) found best [246]
Bael toffee Preservation with sugar New product development Pulp: sugar (1:1) found best [246]
Bael tea Juice extraction Antioxidant activity measurement Antioxidant activity comparable with green
tea.
[234]
Bael beverage Dried powder mixed in water Extension of shelf life 50 ppm KMS, sodium benzoate, citric acid
increase shelf-life up to 50 days
[226]
Fermented fruit
juice
Fermentation New product development Higher DPPH, H2O2 and ABTS activity;
Sensory analysis
[242]
Unripe pulp Bael preserve Preservation with syrup Ayurvedic product development 6 days of preparation with sugar and citric
acid
[64]
Bael preserve Preservation with syrup New product development Pulp: sugar: water ¼ 1:1.25:1 and boiling
operation.
[240]
Dehydrated bael Dehydration New product development 30 min Sulphur di-oxide treatment and
heating at 55–60
C.
[240]
Bael fruit
seed
Seed oil Ultrasonic extraction RSM and ANN modelling Biofuel for fuel cell hydrogen production [232]
Seed cake oil Pyrolysis RSM and ANN modelling Lower carbon mono-oxide emission [237]
Oil Microwave extraction RSM modelling 42.6% oil yield at 340W [231]
Bael peel
and
pomace
Cattle feed Dehydration and grinding Waste utilisation 69.6% pomace and 40.1% peel was digestible [237]
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
5

6. insulin from beta cells present in islets of Langerhans. The mechanism of
action of bael in preventing diabetes can be taken place in various ways
(Fig. 3), such as lowering the glucose level in blood and glycosylated
hemoglobin, thereby increase in liver glycogen in experimental diabetic
rats [4]. Glucose transporter GLUT2, present in β-cells is influenced by
phenolic acids in a way that GLUT 4 transportation is enhanced through
Table 4
Quantitative phytochemical analysis of different parts of bael (Aegle marmelos). Where, TPC ¼ total phenolic content, TFC ¼ total flavonoid content, GAE ¼ Gallic acid
equivalent, CE ¼ Catechin equivalent, dw ¼ dry weight.
Reference Portion of bael TPC TFC Tannin Total Carotenoids Vitamin C Alkaloids
[52] Pulp 87.34 mg GAE/g dw 15.20 mg CE/g dw – 32.98 μg/g dw 26.17mg/100dw –
[8] Alcoholic extract of pulp 158.66 mg/g 166 mg/g 193.33 mg/g – – –
Aqueous extract of pulp 147.66 mg/g 129.0 mg/g 98.66 mg/g – – –
[151] Must 1.02 g/100 mL – – β-carotene
55μg/100 mL
86mg/100 mL –
[15] Pulp 26.3 mg GAE/g dw – – – – –
Pericarp 35.13 mg GAE/g dw – – – – –
[69] Leaf 29.4 mg/g 63.9 mg/g 10.54 mg/g 16.08 mg/g
[59] Flower Ethanol extract- 1615.2 mg GAE/g 1095.7 μg CE/g – – – –
Aqueous extract-1496.7 mg GAE/g 938.77 μg CE/g – – – –
[144] Leaf 16.5 mg GAE/g – – –
Bark 14.2 mg GAE/g – – – – –
Fruit 10.6 mg GAE/g – – – – –
[246] Leaf 2.4 mg/100 g 2.4 mg/100 g β-carotene
8600 μg/100 g
260 mg/100 g –
[180] Leaf 30.34 mg/g 64 mg/g 15.58 mg/g
Leaf 1118.12 mg GAE/100 g –
Fig. 1. Anti-convulsant, Immunomodulatory, contractile, cytoprotective, wound healing and anti-proliferative activities of bael (RBC: red blood cell, NO: nitric oxide,
PPAR: peroxisome proliferator-activated receptor, ROS: reactive oxygen species). (For interpretation of the references to colour in this figure legend, the reader is
referred to the Web version of this article.)
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
6

7. phosphatidylinositol 3-kinase and Akt (Protein Kinase B PI3K/Akt also,
by adenosine monophosphate (AMP) activated protein kinase pathway.
Among phenolic acids, ferulic acid, and chlorogenic acid work in the
same manner thereby function as anti-diabetic agents [60–66]. As
various enzymes namely α-amylase, α-glucosidase convert carbohydrate
to glucose, phenolic acids can effectively inhibit these enzymes [67].
Another experiment has been conducted where the different dosages of
100, 250, 500 mg/kg aqueous extract of bael seeds are orally applied to
different categories rats like a normal rat, fasting blood glucose (FBG),
normal, and mild diabetic rats where FBG- 120–250 mg/dl. The observed
result may be noted as total cholesterol (TC) level lowers by 25.49%,
whereas a hike of 33.43% is observed in high-density lipoprotein (HDL),
on the other hand, 53.97% decrease in low-density lipoprotein and
45.77% in triglyceride (TC) [68]. It is evident from the results that the
aqueous extract of seed possesses anti-diabetic properties [68]. Kar-
unanayake et al., 1984 reported the bael seed extract shows hypoglyce-
mic effects in the case of streptoztocin induced diabetic rats [69].
Vitamin E present in bael shows anti-diabetic effects. Effect of bael leaf
extract has been administered on streptozotocin-induced diabetic rats for
24 h, the analysed result may be explained as aegelin 2 in leaf extract
shows the hypoglycemic effect and can reduce blood glucose level by
16.9% [70]. Among the different compounds isolated from bael leaf,
anhydromarmeline, phenyl ethyl cinnamide compound proves to be the
best α-glucosidase inhibitor [71]. In the triterpenoids group, lupeol has a
potential hypoglycemic effect on streptoztocin induced diabetic rats
[72]. The hypoglycemic activity of aegelin and lupeol in bael extract is
supported by HPLC analysis [66]. Bhatti et al., 2013 have studied the
efficiency of bael leaf extract in diabetic nephropathy on alloxan-induced
diabetic nephropathic rats [73]. Umbelliferon-α-Dglucopyranosyl-(2I →
1II)-α-D-glucopyranoside extracted from bael extract exhibits hypogly-
cemic effect tested in streptozotocin-promoted diabetic rats by reducing
serum glucose, fructose-1-6-biphosphate, glycated hemoglobin,
glucose-6-phosphatase as well as an increment in hexokinase, plasma
insulin [1]. Umbelliferone β-D-galactopyranoside is found to have
anti-diabetic effects in streptozotocin-induced diabetic rats [1]. Other
than these compounds, (3, 3-dimethylallyl) halfordinol also shows anti-
diabetic as well as antihyperlipidemic effect experimented in vitro in
3T3-L1 cells whereas in vivo experiment in high-fat diet-promoted obese
C57/BL6J mice. Anti-diabetic effects with a fall in plasma glucose in
obese mice is also a result of (3, 3-dimethylallyl) halfordinol [74]. A
formulation made with bael, glipizide, an oral antidiabetic drug, with the
other two medicinal plants is tested on streptozotocin-induced diabetic
Fig. 2. Mechanism of antimicrobial activity of bael.
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
7

8. rats for hypoglycemic effect, and it shows outstanding result [75].
Another report on methanolic extract of bael leaf shows a fall in blood
glucose level in Wistar albino rats grouped in different dosages [76].
Methanolic extracts of A. marmelos can promote glucose uptake on the
other hand peroxisome proliferator activator receptor γ (PPARγ), Glut-4
and phosphatidylinositol 3'kinase (PI3 kinase) can transport it [77]. In
the case of diabetic rats induced with streptozotocin, damage due to
oxidative stress may be prohibited by bael extract [78]. Treatment with
umbelliferone, an antioxidant present in bael can reduce prothrombin
which in turn reduces both clottings as well as bleeding time in the case
of streptozotocin-induced diabetic rats [79]. In streptozotocin promoted
rats orally administered Aegle marmelos, Momordica charantia, and Euge-
nia jambolana alcoholic extract taken at a dose level of 250 mg/kg and
500 mg/kg for the one-month duration can effectively reduce serum
glutamic pyruvate transminase activities and serum glutamic oxaloace-
tate transminase [80]. Aegle marmelos leaf extract increases serum insulin
level and thereby decrease blood glucose level [81]. Homeostasis model
assessment of insulin resistance (HOMA-IR), glucose, IL-6, insulin, dys-
lipidemia, TNF-α these parameters come under control with bael extract
treatment for 21 days in spretozotocin-induced rats [1]. Anhy-
dromarmeline aegelinosides A and B found in bael leaf extract act as a
–glucosidase inhibitors [71].
8.3. Anti-microbial activity
Bael is reported to be extraordinary in protection against a wide va-
riety of pathogenic organisms which include antibacterial, antitumor,
antiviral, anti-inflammatory, anti-fungal [1]. Marmelide extracted from
bael have shown antimicrobial activity when experimented with cox-
sackieviruses B1–B6, in an assay described by plaque inhibition assay at
96 h. Without doing any toxic effects to host cells the extract is proved to
have antiviral activity (Fig. 2). In comparison to ribavirin, an
anti-microbial drug, marmelide has been found to have more potential
activity. The virucidal activity of marmelide and extract follows inhibi-
tion at the primary phase of a replicative cycle like adsorption as well as
penetration [82]. Dhar et al., 1968 shows the juice exhibits antiviral
potential against the Ranikhet disease virus [83]. Potential
anti-microbial effect against different diarrhoea causing bacteria like
Vibrio cholera have been observed with chloroform extract of bael root,
other bacteria include Escherichia coli and Shigella sp. agar dilution, disc
dilution methods have been used for determining the activity and may be
compared with the drug ciprofloxacin [40]. In another study by Rani and
Khullar, 2004 Salmonella typhi was also found to be affected by meth-
anolic extract of bael. A. brassicae, Fusarium oxysporum, Ciceris
A. carthami, Alternaria alternate, Colletotrichum capsici, Curvularia lunata,
Fig. 3. Mechanism of antioxidant, anti-diarrehoea, antihyperlipidemic and anti-diabetic activities of bael (SOD: super oxide dismutase, GSH: glutathione).
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
8

9. Ustilago cynodontis, and F. udum these eight pathogens are restricted in a
spore germination assay by the essential oils extracted from bael [84]. At
a dosage of 0.05% of extract all the fungi have been inhibited by 100%,
whereas 0.03% and 0.04% of extract show near about 75%, 90% inhi-
bition respectively [85]. Filariae also found to be prevented with bael leaf
extract [86]. Bael powder has the ability to prevent intestinal parasites
like Ascaris lumbricoides and Entamoeba histolytica [87]. Disc diffusion
assay in which the MIC value is reported as 6.25 μg/disc for Candida
albicans and Aspergillus species have shown anti-microbial activity by
1-methyl-2-(3'-methyl-but-2'-enyloxy)-anthraquinone, an anthraquinone
found from bael seed. Leaf extract oil can reduce aflatoxin produced by
Aspergillus flavus, when added with a concentration of 500 μg/L [88].
(þ)-4-(2'-hydroxy-3'-methylbut-3'-enyloxy)-8H- [1,3] dioxolo [4,5-h]
chromen-8-one and 2-isopropenyl-4-methyl-1-oxa-cyclopenta [b]
anthracene-5,10-dione are the different compounds isolated from bael
have possessed anti-microbial activity [89]. Klebsiella pneumonia, Enter-
cococcus faecalis, Streptococcus faecalis and Micrococcus luteus have been
inhibited by bael fruit juice. In a study, Aeromonas hydrophila Chester has
been inoculated to Cyprinus carpio Linn, a freshwater fish at a dosage of
1.5 104 cells/mL. The chance of fish survival has increased and got
extremely high with leaf extract at a dosage of 5 g/kg body weight.
Haemoglobin level, white blood cell (WBC) count, red blood cell count,
phagocytic activity, lysosomal activity, and pathogen clearance activity
have been noticed to be increased [90]. Dermatophytic fungi namely
T. rubrum, Trichophyton mentagrophytes, M. gypseum, Microsporum canis,
and Epidermophyton floccosum have been experimented with broth dilu-
tion method, with solvents like water-ethanol, methanol of bael with MIC
of 400 μg/mL concentration show protective effect against fungi [91].
Different solvent extracts of bael have been rendering anti-parasitic ac-
tivity. A study of this has been conducted with the larvae of Rhipicephalus
microplus, adult cattle tick Haemaphysalis bispinosa, and sheep fluke Par-
amphistomum cervi in various concentrations of the extract. The result
obtained may be represented as the most toxic effect with a mortality rate
of 100% have been exhibited by 0.3% methanol in case of adult cattle
tick as well as for larvae of Rhipicephalus microplus, and for larvae of
Rhipicephalus microplus the desired concentration is 0.2% [92]. Leaf
extract of bael at a concentration 0.5–2 mg/mL exhibits anti-fungal ac-
tivity [93]. Seeds and leaves of bael show antimicrobial activity against
NK 65 strain of Plasmodium berghei [16]. Different studies verify the
anti-microbial effect of bael extract like disc diffusion method of petro-
leum ether extract brings about the extremely effective result against
Pseudomonas aeruginosa, Staphylococcus aureus, E. coli and β Streptococcus
haemolyticus group A whereas chloroform extract is suitable against
Proteus mimrabilis, Klebsiella pneumonia, different fungi such as A. flavus,
C. albicans and C. tropicalis are mostly prevented by methanolic extract of
bael [94]. In the case of antihuman human immunodeficiency virus
(HIV) study bael extract can potentially decrease the rate of production of
CD4þ
T-cells CEM-green fluorescent protein which is affected by
HIV-1NL4.3 [95]. Green fruit acetone extract produces xanthoarnol,
which is highly protective against Enterococcus faecalis [96]. Agar diffu-
sion method has proved the extraordinary power of bael leaf extract
against various gram-positive like B. cereus, S. aureus, S. epidermidis as
well as gram-negative bacteria namely S. aureus and E. aerogens is mostly
prevented by methanolic extract of bael leaf extract at a concentration of
40 mg/mL [97]. A quinone like compound isolated from bael is found to
be potent against Escherichia coli and P. aeruginosa with (MIC
value-25 μg/mL). A. clavatus, A. niger, Penicillium roqueforti, C. albicans
and A. oryzae are also inhibited by this compound present in bael [98].
Bael, when blended with imipenem, shows extremely potent against the
strains of Acinetobacter baumannii, though alone the antibiotic shows
lesser inhibitory effect. In a study with a different solvent such as
methanol, ethanol, ethyl acetate, petroleum ether, n-hexane, and
dichloromethane extract of bael and essential oils from bael is tested for
microbial action. The disc diffusion method is used in determining
minimum inhibitory concentration. The result obtained proves the
antimicrobial activity of different bael extract against different bacteria
under study [98]. Shahidine an alkaloid present in bael exhibits anti-
bacterial activity against gram-positive bacteria [99]. In another study to
view the antibacterial activity shown by the essential oils present in bael,
the disc diffusion method is used with gram-positive bacteria like
Staphylococcus aureus, Corynebacterium diphtheriae, and Bacillus cereus and
three Gram-negative bacteria: Escherichia coli, Proteus mirabilis, and
Pseudomonas aeruginosa. The result shows the most inhibitory action
against S. aureus followed by C. diphtheriae, E. coli, and P. mirabilis
however negative result is seen against P. aeruginosa [14]. β-lactam-re-
sistant Shigella flexneri and Shigella dysenteriae have been found to be
more susceptible to β-lactam antibiotics [100]. In a study with bael tree
bark to observe the antibacterial activity, the bacterial strains Escherichia
coli, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumonia, Entero-
coccus faecalis, Pseudomonas aeruginosa, and Salmonella enterica subsp.
enterica serovar typhi are used. The antimicrobial activity has been eval-
uated with the agar well diffusion method. The result finds the antimi-
crobial properties of bael tree bark in different solvents like methanol and
hexane [101]. The Agar diffusion method has been employed in esti-
mating minimum inhibitory concentration thus found α-phellandrene
and α-pinene present in bael exhibit antimicrobial activity [102]. Anti-
microbial action has been seen against Salmonella typhi [84]. Enter-
oinvasive Shigella flexneri strains and Escherichia coli are found to be
hardly affected by aqueous decoction in the hot condition of unripe fruit
[2]. Imperatorin, the furocoumarin present in bael can inhibit zinc su-
peroxide dismutase thus Shigella dysenteriae succumbed to oxidative
stress [33].
8.4. Anti-cancer activity
Cancer becomes one of the most critical diseases in the present day.
The treatment procedure, as well as medicines, are very costly [103].
Different compounds isolated from the extract which prove to be
extremely significant in inhibiting K562 cells are butylated hydrox-
yanisole, butyl ptolyl sulfide, and 6-methyl-4-chromanone. An in vitro
experiment for cytotoxicity on medical plants in Bangladesh it confirms
the cytotoxic effects of bael extract on MDA-MB-231 and MCF-7 breast
cancer cells [104,105]. T-lymphoid Jurkat, Leukemic K562, B-lymphoid
Raji, melanoma Colo38, erythroleukemic HEL, and breast cancer
MDA-MB-231 and MCF7 cell these tumor cells may be inhibited by bael
extract [106]. Another study applied bael extract intraperitoneally on
Swiss albino mice affected by Ehrlich ascites carcinoma, in that case,
hydroalcoholic bael extract is used with a dosage of 400 mg/kg. A sig-
nificant result is obtained which reveals the extension of median survival
time for 28 days, quite higher than the control group administered with
saline [51]. Carotenoids, phytochemicals, polyphenols present in bael
may have the ability to reduce cell mutation thus DNA damage is reduced
[107]. It is observed from a study that lupeol present in bael produces a
remarkable effect on the sequence of RA4 DNA by extending ERα
expression in ERα-negative MDA-MB-231 cells thereby be able to cease
the multiplication of cancer cells [105]. By improving the immune sys-
tem of the body bael extract help in anti-cancer activity [108]. When
doxorubicin treatment is applied to mouse bone marrow, the produced
genotoxic effects may be retarded by bael extract. Treatment is done for 5
days at a stretch before doxorubicin is applied, which brings about the
reduction in the increase of normochromatic erythrocyte and micro
nucleated polychromatic frequency produced with doxorubicin treat-
ment [109]. Anti-neoplastic effects have been exhibited by D-limolene,
eugenol, citral obtained from bael extract [110]. Antineoplastic effects
shown by lupeol in bael affects human melanoma 451Lu cells, B162F2
cells, WM35 cells, human epidermoid carcinoma A431 cells, prostate
carcinoma cell lines LNCaP, hepatocellular carcinoma SMMC7721 cells,
human pancreatic adenocarcinoma cells AsPC-120 CWR22R_1 and PC-3.
Lupeol is found to decrease the expression of cyclin D2, cyclin D1, eDk2
thus G1-S phase cell cycle is arrested [111]. In a study the potential of
1-hydroxy-5, 7-dimethoxy-2-naphthalenecarboxaldehyde compound
found in bael extract is checked for its anticancer activity, it is applied to
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
9

10. HEp-2 alveolar epithelial and HCT-116 colon carcinoma xenograft
affected mice, the result explores the cell multiplication is reduced
whereas induced apoptosis is seen in malignant cells in G1 phase during
the cell cycle, which is supported by an incremental level of caspase-3
with arrested cell cycle during the G1 phase [112]. The bael fruit
extract possesses anticancer activity when tested with 7, 12-dimethyl-
benz (a) anthracene (DMBA) - affected skin papilloma genesis in mice.
Papilloma incidence is supposed to be reduced by 70% and 50%
respectively for peri-initiational oral injection and post-initiational oral
injection of bael extract. Not only this also tumor burden, papillomas
number, and tumor yield with respect to the control group treated with
DMBA have been decreased. In the case of DMBA treated mice GSH level
has been restored, superoxide dismutase (SOD), catalase (CAT) activity
are significantly inclined, in skin and liver the lipid peroxidation level is
found to get decreased with the treatment of bael fruit extract. So from
these observations, it may be stated that oxidative stress has fallen and it
is quite effective in skin carcinogenesis treatment. Administration of
methanolic extract of bael gives rise to promote protection against
2-acetyl aminofluorene-promoted and diethylnitrosamine-induced hep-
atocarcinoma rats. Hepatic DNA synthesis, ornithine decarboxylase ac-
tivity in addition to oxidative stress relief with antioxidant enzyme level
increment are the proof of hepatocarcinogenesis progression inhibition
[113]. In a study column chromatography of ethanolic bael extract
produces five fractions, of which furanocoumarin imperatoin is able to
fight with leukemia THP-1 cancer cells [73]. The hydroalcoholic leaf
extract when administered against N-methyl N-nitrosourea (MNU) -
promoted hepatocarcinogenesis in mice, it exhibits anticancer as well as
immunomodulatory, hepatoprotective effects. By increasing neutrophil,
leukocyte, and monocyte counts and lowering inflammatory cytokines as
IL-1β and IL-6 work effectively, it also reduces tumor gene p53 as well as
anti-apoptotic gene Bcl-2 in comparison to the MNU-induced group. In
the MNU-administered group, the Raman spectrum shows peak intensity
at a frequency 1252 cm1
but it is not found in the control group treated
with phosphate buffer saline, which is evident for the anticancer activity
[32]. In another study, mice affected with Ehrlich’s carcinoma, Dalton’s
lymphoma ascites, and Dalton’s lymphoma ascites are treated with
petroleum ether extract of bael. It is observed that lymphocyte prolifer-
ation, hematopoiesis WBC count, macrophage count are boosted up. The
extract may also be effective in increasing survival time, on the other
hand, the ascites tumor volume, tumor counts get reduced. This result
may be compared to 5-flurouracil or cyclophosphamide taking cancer
group. Immunocompromised patients may be highly recommended by
taking xanthorrhizol and marmelosin, isolated from bael instead of
chemotherapy [114]. Bael peptic polysaccharide has been tested for skin
cancer activity [115]. Antioxidant and chemopreventive actions may be
exhibited by bael barks extract on swiss albino mice induced with pap-
illoma and DMBA [116].
8.5. Cardioprotective effect
Various cardiovascular diseases may be listed as myocardial infarc-
tion atherosclerosis and hypertension. Methanolic bael root bark extract
at a dosage level of 100 μg/mL can reduce up to 50% of the heartbeat rate
[24]. Several risk factors are associated with these diseases like
cell-derived microparticles and hypercholesterolemia [117,118].
Different medicinal plants are supposed to be effective against fighting
these diseases with inhibition of lipid peroxidation and decrease the level
of low-density lipoprotein [117–119] and enhancing endothelial
dysfunction [120]. Bael fruit is found to have protective against cardio-
vascular diseases. Linear furanocoumarin marmesinin, a bioactive com-
pound present in bael has the ability to lowering lipid peroxidation
(Fig. 5). This is because dosage of 200 mg/kg exhibits antioxidant effect
when tested with male albino Wistar rats which have isoproterenol
promoted myocardial injury. Enhancement of different enzymes for
example creatine kinase-muscle/brain (CK-MB), lactate dehydrogenase
(LDH) isoenzyme, creatine kinase, LDH may be retarded by a compound
marmesinin [121]. Serum LDH and CK levels are decreased on the other
hand when leaf extract of bael with a dosage of 200 mg/kg is applied to
isoprenaline induced myocardial rats the level is enhanced. Not only had
that some other biochemical parameters are also found to get increased
[122]. Another study on isoproterenol-induced myocardial infarction
rats which shows the leaf extract is effective against cardiac marker
Fig. 4. Mechanism of antispermatogenic activities of bael.
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
10

11. enzymes, the effect may be similar to uptake of 60 mg/kg α-tocopherol. A
study on doxorubicin-induced rat, periplogenin, a compound isolated
from bael is observed to show cardiovascular protection when used at
25 mg/kg. Cardiac as well as hepatic biochemical markers level may
come to a normal level with periplogenin treatment, that effect is similar
to the treatment of α-tocopherol [123]. About 30% of mortality around
the world could be due to cardiovascular diseases [124]. A study with
bael extract in different solvents namely aqueous, alcoholic, petroleum
ether show different cardioprotective actions like aqueous extract ex-
hibits smooth muscle relaxant, cardiac stimulant on the other hand
alcoholic extract show cardiac depressant activity, uterine relaxant ac-
tivity [58]. The cardiotonic activity of bael has experimented on isolated
frog heart assembly with a different dilution of bael extract. Bael extract
proves to be better than digoxin [125]. Different phytochemicals (ter-
penoids, tannins, flavonoids) present in bael have the ability to protect
the heart from isoproterenol promoted myocardial infarction [126].
8.6. Anti-hyperlipidemic activity
Bael extract is reported to be able to reduce the lipid level. The
antihyperlipidemic effect has been exhibited by bael extract [122]. This
may be supported by an experiment on streptozotocin-promoted diabetic
rats. Various parameters that are taken into consideration involve tri-
glycerides (TG), serum total cholesterol (TC), high-density lipoprotein
(HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein
(VLDL). The rats under study have been administered with aqueous bael
extract with a dosage of 250, 350, and 450 mg/kg body weight in an
increasing manner. The result shows a significant anti-hyperlipidemic
effect if compared to the diabetic control group [127]. The lipid profile
of serum may be controlled with aqueous bael extract in a test with
streptozotocin-promoted rats. Triglyceride hydrolysis has started which
causes a decrease in blood cholesterol levels which may be a result of the
transportation of fat from adhered adipose tissue [52]. From the study, it
is concluded that umbelliferone present in bael exhibits anti-
hyperlipidemic activity (Fig. 3). Saponins and coumarins in bael leaf
extract can reduce the cholesterol level [79]. Free cholesterol levels as
well as ester cholesterol level has been reduced with bael fruit powder
[158]. Fasting blood glucose or FBG diabetic rats are treated with
250 mg/kg aqueous bael seed extract which results in a reduction of
blood glucose level by 60.87% [68]. TC has been decreased (25.49%) and
a 33.43% increment in HDL is seen. On the other hand, a reduction of
53.97% in LDL and 45.77% in TG have resulted from the experiment
which supports the antihyperlipidemic activity of bael. Plasma TG has
been reduced by 55%, total cholesterol by 24%, 24% free fatty acid, 28%
increase of HDL-C in the dyslipidemic hamster model with a dosage of
50 mg/kg body weight [70]. Another study on Triton WR 1339 admin-
istered rats the ethanolic bael leaf extract can reduce serum cholesterol
and TG level at a dosage of 125 and 250 mg/kg [128].
8.7. Anti-ulcer activity
The ulcer is nowadays a very common disease of the gastrointestinal
tract. Reasons behind ulcer may be listed as oxidative stress, Helicobacter
pylori bacteria when gastroprotection is reduced or mucosal flow of blood
get inhibited [129]. Luvangetin, a pyranocoumarin present in bael seed
shows protective activity against aspirin-induced and pylorus-ligated
gastric ulcers experimented on rats [130]. Another study reveals fruit
pulp extract when used in treating albino rats there is a fall in mucosal
thickness, catalase activity, and superoxide dismutase and also in gluta-
thione level. Lipid peroxidation activity, Ulcer index, alanine amino-
transferase, aspartate aminotransferase have also been increased thus the
antiulcer activity of bael is largely dependent on the antioxidant mech-
anism (Fig. 7) [131]. Anti-ulcer activity exhibited by bael has been re-
ported in different studies. Gastric ulcer induced by lipopolysaccharide in
rats has been administered orally with methanolic extract of bael [132].
The study has shown the effectiveness in reducing gastric ulcers by
93.98% with a dosage of 500 mg/kg methanolic extract of bael. The
reason behind this may be explained as gastric parameters are largely
restricted which include the volume of gastric juice, pepsin concentra-
tion, free and/or total acidity, and acid output. Single-dose aspirin at a
dosage of 500 mg/kg rat body weight is induced to rats to study the
antiulcer effects of bael fruit extracts of 250 mg/kg rat body weight. This
pre-treatment is done for two weeks before the treatment of aspirin has
started. Two observations may be concluded from the test, one is for the
single-dose aspirin-treated group, in that case, the mean ulcer index
(MUI) has increased whereas serotonin content has seen a decrease with
lower enterochromaffin cell number and also adhering mucous layer also
get decreased. On the other hand for another group that has been
Fig. 5. Cardio protective, neuro-protective and hepatoprotective activities of bael (LDL: low-density lipoprotein, LDH: lactate dehydrogenase, CAT: catalase, MDA:
malondialdehyde).
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11

12. previously treated with bael fruit extract shows a fall in MUI but an
increment in the enterochromaffin cell number as well as serotonin
content and also mucous membrane thickness. Antiulcer activity
experimented over albino rats for bael fruit extract has also been done by
Ref. [133]. Another study on unripe bael fruit extract show
gastro-protective activity applied for mucosal damage induced by
ethanol, but the activity has not been seen in the case of indomethacin or
hypothermic induced restraint stress in rats. It may be concluded from
the result that the gastro-protective mechanism does not follow the
prostaglandin pathway [42]. A few intestinal bacteria such as S. boydii, E.
coli, S. flexneri and S. sonnei against those antibacterial activities of dried
bael fruit pulp has been monitored in colitis affected rats promoted by 2,
4,6-trinitrobenzene sulfonic acid (TNBS). After 2 weeks of colitis treat-
ment methanolic extract of bael has shown lowering in colonic inflam-
mation as well as mucosal damage, free radicals are restricted and
myeloperoxidase level inducted by TNBS has also get reduced. Sulfasa-
lazine, a medicine used against colitis may be comparable with bael
extract anticolitis activity when the medicine is taken at a dosage of
100 mg/kg [134]. Ghatule et al., 2014 have shown that soaked bael leaf
water is helpful against cancer [135]. A formulation made up of Gly-
cyrrhizia glabra rhizome part (200 mg), bael leaf part (150 mg), Hemi-
desmus indicus root part (75 mg) and Cumimum cyminum fruit part
(75 mg). The anti-ulcer activity has been exhibited by this formulation
with a dosage of 500 mg/kg [136]. A study on indomethacin-induced
ulceration, as well as stressed induced ulceration also pylorus ligation
induced ulcerations, have been studied to see the anti-ulcer action of bael
fruit seed. In pylorus ligated rats a fall in gastric juice, total acidity, and
free acidity are observed with a rise in pH. Both methanolic and aqueous
extract has possessed anti-ulcer activity due to the presence of phyto-
chemical quercetin in bael [137].
8.8. Antipyretic or anti-inflammatory activity
In the case of foreign particles or pathogens attack, inflammation in
body parts is one of the defense mechanisms opted. Pain, swelling,
redness, or heat may be the signs of inflammation [47]. In
carrageenan-induced paw oedema analgesic activity has been observed.
Fig. 6. The mechanism for radioprotective activity of bael.
Fig. 7. The anti-ulcer activity of bael (NSAID: Nonsteroidal anti-inflammatory
drug, ROS: reactive oxygen species).
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13. The same may be seen in cotton-pellet granuloma also. The presence of
lupeol, citral, skimmianine may act as anti-inflammatory agents
following histamine-mediated signalling [138]. Other observations may
include a lowering of hyperpyrexia and also, paw licking in mice in their
early and late phases. These are the pieces of evidence of antipyretic and
analgesic activity of bael leaf extract [139]. In a study where the mos-
quito larvicidal activity is taken into consideration, bael aqueous leaf
extract with phytofabrication of nickel nanoparticles proves to be more
potent than leaf extract alone [140]. β caryophyllene and caryophyllene
oxide found from bael extract have shown an anti-inflammatory effect
against lymphoma as well as neuroblastoma cells. This action follows the
mechanism of up-regulating the pro-apoptotic genes also downregulating
anti-apoptotic genes [141]. In studying the anti-inflammatory action of
dried flower extract of bael, the optimum dosage is noted to be
200 mg/kg when experimented on Wistar rats [142]. The antipyretic
effect of bael has been seen in Brewer’s yeast-promoted pyrexia in albino
rats [12]. Ethanolic extract of bael exhibits the power of lowering
increased body temperature with a dosage of 200 and 400 mg/kg [12].
Bael fruit extract exhibits actions like anti-inflammatory, mast cell sta-
bilization, and antioxidant along with superoxide dismutase increase and
malondialdehyde level decrease which gives protection for degranula-
tion in must cells [143]. The bark of the bael tree root possesses a strong
anti-inflammatory action when tested with carrageenan-induced paw
oedema [144]. A study on young roots of the bael tree shows the potent
anti-inflammatory effects in cyclooxygenase (COX-2) inhibition, restricts
pro-inflammatory cytokine [145], in vitro study with bael leaf extract
shows the anti-inflammatory effect at a dose of 100 μg/mL [146]. Mar-
melosin extracted from bael fruit possesses an anti-inflammatory effect
with a reduction of nitric oxide (NO) as well as TNF-α which is a
pro-inflammatory cytokine [115]. In another study with methanolic
extract of bael, it shows analgesic activity centrally as well as peripher-
ally. In the acetic acid-induced animal model, the dry ripe fruit is found to
be a more effective tail-flick radiant heat model. In pain disorder, bael
can act as an effective remedy [147]. Bael at a dosage 200 and 300 mg/kg
exhibit analgesic activity applied on acetic acid-promoted writhing and
tail-flick tested in mice [148].
8.9. Hepatoprotective activity
The bael leave extract with a concentration of 25 mg/kg shows the
most effective result against doxorubicin-induced hepatotoxicity [123].
In a study with diabetic rats induced with streptozotocin, it is observed
that the changes in hepatic parameters have come to a normal level, these
parameters include liver fibrosis, dilation of veins, an arrangement of
hepatocytes, depletion of characteristic concentric, and reduction of
glycogen content [149]. In studying the hepatoprotective action of bael,
rats are induced with a 5 106
colony-forming unit (CFU)/0.1 mL
dosage of bacterial suspension intraperitoneally. After 15 days of
observation, they are kept in fasting for 12 h, in between subjected to
100 mg/kg saline then exposed to chloroform anaesthesia. Parameters
such as protein 56, Serum glutamic oxaloacetic transaminase (SGOT),
alkaline phosphate, Serum glutamic pyruvic transaminase (SGPT) 54
from total bilirubin 55 have been analysed after treating the organs with
ice-cold saline. Then the rats are treated with 30% ethanol for 40 days
and then with bael leaf powder for 21 days. It shows an amazing effect
[150]. In a study where rats and mice are fed with bael in a dose of 25 and
50 mg/kg for 7 days and after that they are induced with carbon tetra-
chloride (CCl4). Observations include lowering of lipoprotein X (LPx),
xanthineoxidase as well as serum toxicity marker enzymes (SGOT, LDH,
SGPT) have also released which is an indication of the hepatoprotective
action of bael [113]. Bael fruit pulp is judged for CCl4 induced hep-
atoprotective activity in pre and post-treatment manner by Ref. [151].
Liver damage markers such as SGOT, SGPT, Alkaline phosphatase (ALP),
and bilirubin are decreased by a good amount in CCl4 only groups.
Post-treatment scores well than pre-treatment schedule. The reverse
result is found for bael seed experimented in the same way [110].
Eugenol extracted from bael leaf has been found to exhibit hep-
atoprotective activity [152]. The hepatoprotective effect of bael has been
further supported by the investigation where they have fond rutin pre-
sent in bael possibly the reason behind the said activity (Fig. 5). Here the
increased TNF-α level has reduced, also the effectiveness is similar to the
action of silymarin. Piperine in combination with bael extract has shown
effective results against CCl4 administered liver problems [153]. Acid
soluble cytochrome P450, sulphydryl (SH) content, nicotinamide
adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase,
DT-diaphorase, cytochrome b5, NADH-cytochrome b5 reductase, super-
oxide dismutase, glutathione reductase, glutathione S-transferase cata-
lase, and glutathione peroxidase basal level in the liver have been
increased by hydroalcoholic bael extract [154].
8.10. Radioprotective effect
Radiotherapy in recent years has been used extensively in the treat-
ment of cancer. But it also offers some side effects. To explore the
radioprotective activity of bael, the hydroalcoholic extract of the fruit is
given to mice who are in exposure to gamma radiation. The extract in
different concentrations 5, 10, 15, 20, or 40 mg/kg is administered
intraperitoneally for 5 consecutive days. After that, they are exposed to
10 Gy 60 Cobalt (Co) gamma-radiations. On day 10 or 30 most of the
survivors are found. The optimum effect has been found at a concen-
tration of 20 mg/kg. After 30 days of treatment, it has been found that
bael extract possesses a radioprotective effect [47,51,103]. It is believed
that the radioprotective action of bael is a result of the scavenging of free
radical and lowering lipid peroxidation (Fig. 6) [1,51,103]. Bael leaf
extract is found to show a better result than fruit extract [110]. Besides
the detrimental effects of ionization of DNA other indirect effect includes
the generation of reactive oxygen species (ROS) [155]. Depletion of cell
pool, altered cell division, cell deaths are the after effect DNA damage
[156]. Bael leaves as well as bael fruit have potential free radical scav-
enging activity [157]. The anticlastogenic behaviour of bael is supported
by an experiment on the prevention of DNA damage in mouse bone
marrow cells and in cultured human peripheral blood lymphocytes [50].
In a study on human peripheral blood lymphocytes to see the effective-
ness of bael in radioprotective effect with a dosage of 5 μg/mL leaf extract
the frequency of lymphocytes is reduced in comparison to the control
group [158]. If bael extract is injected before the irradiation exposure
then it is observed that lipid peroxidation is decreased [158]. Loss of
immunity is one of the results of radiation. Bael leaf extract is able in
increasing the splenic lymphocyte count experimented on mice, thereby
proving the immunomodulatory action of bael [110]. Bael has a pre-
venting action against gastro-intestinal (GI) cells. Gamma radiation of 7
gray dosages is administered to animals. Damage is found to have
maximum effect on day 1 of post-treatment whereas recovered on day 7
of post-radiation [157]. Post radiation day 1 and day 7 shows lymphocyte
count, hemoglobin, leukocyte counts have increased with the adminis-
tration of bael leaf extract [157].
8.11. Anti spermatogenic activity
It is required for sperm to pass through epididymis caput, corpus, and
cauda for maturation [159]. Bael leaf may decrease the motility of sperm.
The spermatogenesis process is restricted by the use of bael leaf [160]. In
an experiment with male rats, the bael leaf extract is administered with a
dosage of 200, 400, and 600 mg/kg. The result shows a huge reduction in
sperm count in rats. Epididymal sperm concentration and sexual
behaviour have been observed to be changed [161,162]. Another study
with bael leaf extract injected at a dosage of 50 mg/100 g body weight in
rats produces a lowering of testicular steroidogenic enzymes. Not only
that also wet weight taken for sex organs has also reduced in comparison
to control. In the seminiferous epithelial cell cycle at stage VII cell
numbers are reduced with leaf extract treatment. The dosage level does
not have any harmful effects on the liver and kidney [163]. A similar
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14. result has been found in the study of Das et al., 2012 [133]. Similar re-
sults are found where leaf extract is administered daily with a dosage of
250 mg/kg and 350 mg/kg for 45 days [164]. Another study has sup-
ported the antispermatogenic activity of bael bark extract. It has been
administered of dosage 200 mg/kg and 400 mg/kg body weight which is
effective from 60th day and 600 mg/kg effective from the 40th day. This
effect is thought to be a result of the presence of marmin and fragrance in
bael which keeps on storing in sex organs. Changes in sperm functioning
lead to infertility [165]. The ethanolic bark extract of bael possesses the
ability to completely inhibit sperm motility. This results in epididymal
sperm density, acrosomal integrity, and degeneration of germinal
epithelium. Bael extract functions during the preimplantation stage and
loss of preimplantation lead to infertility [166]. Bael destroys the
viability of sperms by inhibiting the calcium channel (Fig. 4) [167–169].
8.12. Wound healing activity
The wound healing technique comprises different steps namely
inflammation, the proliferation of the cell, and contraction in the for-
mation of collagen lattice. Reddening, pain, oedema are basic symptoms
associated with wound and also occur during inflammation. The release
of reactive oxygen species is found to be a defence mechanism [170].
Experiment on excision model Wistar rats have been administered with
methanolic extract of bael seed ointment. From the day of wounding it is
monitored on days 0, 4, 8, 12, 16, and 20. It is seen that the ointment can
effectively heal the wound completely [171]. Ehrlich and Hunt's model
has been used in male Wistar rats. The treatment is continued with the
bael extract ointment for 10 days and after the 9th day using Lee method
the wound is measured using a tensiometer. In comparison to control it
has been noticed that in the excision model wound healing has taken
place in a better way. Tensile stress in the incision model has reduced
which is proof of wound healing activity of bael [172]. This wound
healing activity of bael is comparable with nitrofurazone drug [204]. The
incision and excision wound healing model applied to albino rats show
wound healing activity of bael pulp extract. SOD, CAT, GSH, lipid per-
oxidation (LPO), NO, and myeloperoxidase (MPO) status study reveal
that bael extract has antioxidant activity, reduce MPO level and free
radicals thus support the healing process (Fig. 1). The bioactive com-
pounds are supposed to be responsible for wound healing activity [19].
Another study on bael extract on excision and incision model proves that
bael possesses wound healing activity. Bael comprises flavonoids, alka-
loids, essential oils, and sterols, these phytoconstituents are the reason
behind the wound healing activity of bael and cause an increased rate of
epithelization, wound contraction, tensile strength, and hydroxyproline
content [20,173].
8.13. Immunomodulatory effect
Fig. 1 represents the possible reason for the immunomodulatory ac-
tivity. Two tests namely carbon clearance assay and neutrophil adhesion
test have been conducted in finding out the immunomodulatory effect of
bael. Oral administration of bael extract on Wistar albino rats has been
done for 14 days then blood sample from retro-orbital plexus has been
collected into heparinized vials and analysed for differential leukocyte
count (DLC). Initially, blood samples are counted and then kept in in-
cubation at 37
C for 15 min. Then the neutrophil index of blood samples
is found by both total leukocyte count (TLC) and DLC. Neutrophils are
being adhered to nylon fibers with which the blood cells are incubated.
The results show a fall in neutrophil count [174]. Phytogenic index
during carbon clearance assay and increase of neutrophil adhesion take
place at a dosage of 500 mg/kg [175]. In a study for mice lethality test as
well as indirect haemagglutination assay has been employed in deter-
mining in humoral immunity. Fruit extract doses are administered orally
at 100 mg/kg and 500 mg/kg. Ocimum sanctum (OSE) at 100 mg/kg has
taken as standard. Phytogenic index and neutrophil adhesion both have
increased significantly. Mortality induced by bovine Pasteurella multocida
in mice has been prevented at both high and low dosage. Low dose
administration is more powerful in the cellular immunity model than a
high dose [174]. In another study on Cyprinus carpio, a freshwater fish
has been infected with aeromonadaceae, and orally it has been admin-
istered at a dosage of 1.5 104
cells/mL. Study on immune response,
enzyme activity against pathogens has been observed for 20 days at a 5
days interval. Enzyme activity, red blood cell count, lysozyme, white
blood cell count have been found to be enhanced in comparison to the
control group. The chance of survival has also been more in bael leaf
administered fish [176]. Another study of ethanolic bael extract has been
found to increase the human Peripheral blood mononuclear cell (PBMC)
and also from the dye exclusion method is also found to be non-toxic. The
immunomodulatory effect of bael has been supported by SRB and (3-(4,
5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay
[177]. Patel et al., 2010 have revealed immune activity by haemagglu-
nation test [174]. In an experiment with Catla catla fish, the bael extract
is found to show the immunomodulatory effect. The highest phagocytic
ratio has been found in a dosage of 25 mg/kg in diet [90].
8.14. Anti convulsant activity
Convulsion is associated with a brain disorder in which a sudden
contraction of the muscle is noticed. A study shows when oral adminis-
tration of bael extract has been done to mice at a dosage of 100 mg/kg
and 200 mg/kg to mice. Hind limb tonic extensions (HLTE) showing
preventive effects in pentylenetetrazole (PTZ) promoted seizure.
Maximal electroshock seizure (MES) and PTZ induced convulsion may be
delayed with the treatment of ethanolic bael extract. Thus gabanergoc
mechanism has been interfered with it and giving the anticonvulsant
effect (Fig. 1). Flavonoids present in bael are found to be responsible for it
[177]. In another study, bael extract can reduce post-traumatic seizures
(PTS) and MES induced convulsion. Post-ictal depression in mice has
been decreased with bael [73].
8.15. Antidepressant activity
Depression is one of the mood-related disorders. Although synthetic
drugs are found to be effective against depression it comes with some
other adverse effects also. Drowsiness, ataxia with benzodiazepines, and
insomnia, libido with selective serotonin reuptake inhibitors are the
problems associated with drugs. In contrast, natural sources as anti-
depressants show fewer side effects [178,179]. Anti-depressant activity
of bael has been reported in mice with anxiolytic drugs using the tail
suspension test and elevated plus maze test. The parameters that need to
be checked are the number of entries into, a number of stretches attend
posture and number of head dips in arms of the elevated plus-maze, time
spent on, and immobility duration in the tail suspension test. Mono-
amines' level has decreased at the postsynaptic site. Antidepressant ac-
tivity of imipramine and fluoxetine have been increased [94]. The
agonistic action of bael on the serotonin receptor forms the basis of the
antidepressant activity of bael [180].
8.16. Anti-genotoxic effects
Genetic materials like DNA, RNA in cells may be damaged by different
substances, in genetics, this is known as genotoxicity. Dietary ingredients
used in chemoprotective agents following the destruction of ROS thus
damaging DNA. Having different phytochemicals bael extract with
different solvents show antigenotoxic activity [73]. Anti-genotoxic
agents are those which have a preventive action against toxic elements.
The anti-genotoxic activity shown by bael is thought to be the poly-
phenolic compounds present in bael. In comet assay on peripheral blood
lymphocyte and use of E. coli PQ37 (SOS chromotest) has been done to
find out the anti-genotoxic effect of bael. In SOS chromotest hydrogen
peroxide-induced SOS and aflatoxin B1 have been reduced in SOS
response. The prevention of DNA from reactive oxygen species has been
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15. done by the presence of polyphenol [181]. In another study with dox-
orubin induced mice, bael extract at different dosages of 200, 250, 300,
350, and 400 mg/kg has been orally administered for five days. It has
been noticed that Micronuclei frequency has been reduced [109]. In
another study, it is found that 250 mg/kg of bael extract has shown the
highest activity against doxorubin-induced genotoxicity [43].
8.17. Anti-proliferative effect
The anti-proliferative action of bael against different human tumor
cells has been reported. In support of this in an experiment where cells
are allowed to grow in the carbon-di-oxide incubator with 24 h incuba-
tion and then they are transferred to a complete growth medium with
further incubation of 48 h. The reason behind the inhibition of in vitro cell
growth of human K562 cells is the identified molecules butyl p-tolyl
sulfide, butylated hydroxyanisole, 6-methyl-4-chromanone. The effec-
tiveness of proliferation is similar to anti-tumor drugs namely cisplatin,
chromomycin, cytosine arabinoside, and 5-fluorouracil [182].
8.18. Anti-microfilariae
Filariasis is caused by parasitic worms belongs to the family filaridea.
Vitex negundo L root extract and bael leave extract at a concentration of
100 ng/mL can be effective in motility loss microfilariae [86]. A dosage
of 100 ng/mL is 100% effective against Brugia malayi [86].
8.19. Anti-histaminic effect
In testing the antihistaminic activity of bael on rat mast cells two cell
lines namely rat peritoneal mast cells (RPMCs) and rat basophilic leu-
kemia (RBL-2H3) are used. To release histamine from rat mast cells
DNP24-BSA, ionomycin, thapsigargin, compound 48/80 have been
applied. Skimmianine present in bael can effectively prevent histamine
release by following the mechanism- DNP24-BSA, thapsigargin, ion-
omycin induced RBL-2H3 cells are affected by Skimmianine [183].
8.20. Contractile activity
Alcoholic extract of bael at a dosage of 1 mg/mL and 2 mg/mL can
exhibit contractile activity in the ileum, tracheal chain isolated from
guinea pig. Fig. 1 depicts the mechanism for the contractile activity of
bael. Maximum relaxation has been shown due to depression occur in the
H1 receptor [139].
8.21. Cytoprotective effect
In a study with Cyprinus carpio, the freshwater fish has been kept for a
period of 1, 8, 16, and 32 days in sub-lethal metal ion concentration. Bael
powder at a dosage of 500 mg/kg is administered to fish after 32 days.
Plasma membrane stabilization as well as antioxidant enzyme system
modulation is proof of the cytoprotective effect of bael [184]. A study
reveals that ROS produced due to oxidative stress can attack RBC and in
turn release hemoglobin (Fig. 1). Bael can effectively produce RBC pro-
tection against oxidants thus confirming the cytoprotective activity
[115].
8.22. Anti-stress activity
Swimming endurance, as well as post swimming motor function test,
forced swim test, and cold swimming endurance test, have been used in
studying the anti-stress activity of bael in albino rats [185]. In the forced
swim model to see the adaptogenic activity of bael, the serum cholesterol
and triglyceride level have not increased but an increase in swimming
endurance time has been noticed and also rota rod falling time and
spontaneous motor activity. The increase in these markers can be
reduced during stress [186]. Another study shows immobilization stress
can do oxidative damage to plasma, kidney, and liver. As the plasma
corticosterone, glucose level has increased and non-enzymatic antioxi-
dants get depleted. Bael extract has the ability to increase plasma corti-
costerone, glucose level, and decrease non-enzymatic antioxidants.
Vitamins C and E present in fruit can effectively reduce stress [74].
8.23. Anti-malarial activity
Trager and Jensen's method has been employed in finding out the
anti-malarial activity of bael root extract against Plasmodium falciparum
(K1, multidrug-resistant) [187]. Quantitatively in vitro anti-malarial ac-
tivity has been done using the method described in Desjardins et al., 1979
[188] inhibitory concentration (IC50) shows that 50% decrease of
parasitic growth due to in vitro regulation of [3H] – hypoxanthine to
P. falciparum. Leaf and immature bark extract of bael show antimalarial
activity against Plasmodium falciparum (IC50–48.2 μg/mL) [189]. The
decoction of root barks may be used for treating malaria [190].
8.24. Anti-arthritis activity
In a rat model that is induced with collagen, anti-arthritis activity has
been noticed. Radiologic and histopathologic changes are observed in the
study. Another study reveals the anti-arthritis activity of bael. Steroids,
saponins, and alkaloids present in bael can retard articular swelling
lowering arthritic index in arthritic rats. Cyclooxygenase enzymes are
inhibited which in turn retard prostaglandin synthesis which is a reason
for arthritis [12].
8.25. Nephroprotective activity
The nephroprotective activity of bael leaf extract has been obtained in
Wistar rats. Increased serum creatinine, blood urea nitrogen level are the
proof of gentamicin nephrotoxicity. Gentamicin can increase the MDA
level also decrease catalase, glutathione levels. Bael extract can effec-
tively reduce the increased MDA level, increase serum creatinine, blood
urea nitrogen level. This proves the nephroprotective activity [191].
Another study supports the nephroprotective activity of bael leaf which is
effective against cisplatin promoted nephrotoxicity [192].
8.26. Anthelmintic activity
The Indian earthworm model is used for the anthelmintic activity of
bael. Aqueous dried bael fruit extract of different concentrations 1, 2, 10,
20 mg/mL are administered to earthworms after washing with distilled
water. At 1 mg/mL concentration a difference is observed in paralysis
and death time when compared to the vehicle control group [166].
8.27. Anti-asthmatic activity
Leaf decoction of bael is effective in reducing phlegm in cold and
asthma. Studying with guinea pig ileum, the tracheal chain it shows an
antagonistic effect on contraction evolved by histamine [139,190]. The
presence of aegeline in bael leaf helps to prohibit the release of histamine
from mast cells [177]. Intracellular Caþþ
signalling events and type of
mast cells affect histamine release. Another study proves that skimmia-
nine present in bael roots takes part in the release of histamine from rat
mast cell [193].
8.29. Anti-thyroid activity
Scopoletin (7-hydroxy-6-methoxy coumarin), found from bael leaf
has been studied for hyperthyroidism. The concentration of scopoletin of
1 mg/kg for 7 days is administered to thyroxine treated animals, reducing
thyroid hormones level in serum. Propylthiouracil, the antithyroid drug
has the same activity as bael extract [143]. Another study finds Aegle
marmelos (1.00 g/kg), Bacopa monnieri (200 mg/kg) and Aloe vera
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16. (125 mg/kg) leaf extracts can effectively show anti-thyroid activity
[194].
8.29. Anti-ocular hypertension activity
Intraocular pressure (IOP) lowering activity has been observed in
rabbits [195]. From baseline IOP a reduction of 22.81% has been seen
with fruit extract at a dosage of 1%. This may be compared to timolol.
The chloroform extract of bael leaf at a dosage 150 and 300 mg/kg
bodyweight has been used against cataract by increasing glutathione,
catalase, and superoxide dismutase and inhibiting lens aldose reductase
(AR) and lowering osmotic stress [196,197].
8.30. Insecticidal activity
Larvae of Japanese encephalitis vector, malaria vector Anopheles
subpictus, and Culex tritaeniorhynchus can be destroyed by the use of bael
extract [198]. Ovicidal, oviposition-deterrent, and repellent activities of
indigenous plant extracts have been done by bael leaf extract which is
effective against Anopheles subpictus [199]. Oviposition repellence
applicable to acetone, methanol, ethyl acetate extracts of bael at a dosage
level 500 ppm are recorded as 92.60%, 93.04%, 95.20%, and the same at
31.25 ppm are recorded as 47.14%, 58.00%, and 56.52% respectively
[199]. The oviposition activity index for ethyl acetate, methanol, acetone
extracts of bael at a dosage of 500 ppm are recorded as 0.86, 0.87,
0.90 respectively. But 100% of mortality has been achieved with
1000 ppm bael extract. A moderate level of adult emergence inhibition
effects is seen for malarial vector Anopheles subpictus with 1000 ppm
concentration exposed for 24 h [200]. A significant effect as a potential
repellent, ovicidal, and oviposition deterrent against Culex htritaenio-
rhynchus has been exhibited by bael extract and Andrographis paniculata
[92]. 500 ppm of methanolic extract of bael can be effective against Culex
tritaeniorhynchus. 100% effectiveness has been exhibited by acetone
extract of bael at a dosage 250 ppm [201]. Larvae of Aedes aegypti and
Anopheles stephensi mosquito can be moderately controlled by methanolic
bael leaf extract [202].
8.31. Toxicological studies
Studies over the toxicological effects of consumption of bael have
reported no such effects and are found to be safe. A dosage of 250 mg/kg
bodyweight of bael extract has been administered to animal for 30 days
but any report on toxic effects has not been found [158]. Pathological
reports suggest that any histopathological changes have not been
exhibited by long term consumption of bael. In Ames assay, the report
reveals that bael being non-mutagenic to TA 100 strain of Salmonella
typhimurium [203]. According to Veerappan et al., 2007, intraperitoneal
administration of 50 mg/k bodyweight of bael extract has not shown any
histopathological changes of liver, kidney, heart, testis, and brain [4,
204]. Lethal dose (LD50), acute and sub-acute values are determined for
rats when tested with aqueous, methanolic, ethanolic extract of bael and
no adverse effect have been observed when 50 mg/kg body weight
intraperitoneal administration is done for 14 days [4]. Other studies
reflect the non-toxic behaviour of bael leaf extract has been administered
intraperitoneally with a dosage of 50, 70, 90, and 100 mg/kg body
weight to male and female Wistar rats for 14 days at a stretch [4]. In an
Table 5
In-vitro antioxidant activities of different portion of bael (Aegle marmelos). Where, DPPH ¼ 2, 2-diphenyl-1-picrylhydrazyl, ABTS ¼ 2, 2’-azino-bis (3-ethyl-
benzothiazoline-6-sulfonic acid, FRAP ¼ Ferric Reducing Ability of Plasma, AAE ¼ Ascorbic acid equivalent.
Part In-vitro Antioxidant activity (IC 50) Reference
DPPH Reducing power Nitric Oxide Super oxide radical ABTS radical [8]
Pulp (Aqueous) 92.648 158.995 98.680 91.410 37.11
Pulp (Alcoholic) 106.158 283.0678 106.243 147.85 35.02
In-vitro Antioxidant activity (IC 50)
DPPH Lipid peroxidation (Egg yolk) Ferrous Ion chelating Ferric Ion chelating Lipid peroxidation (ferric thiocyanate) [15]
Fruit (Methanolic) 0.046 2.14 1.53 1.32 1.87
In-vitro Antioxidant activity (%)
DPPH Hydoxyl scavenging Liposome peroxidation Ferrous Ion chelating [59]
Flower (Aqueous) 50.5 41.5 81.1 20.4
Flower (50% ethanol) 59.5 26.5 77.3 16.9
In-vitro Antioxidant activity (%) [73]
DPPH
Leaf 64.12
Stem 76.883
Root 64.193
In-vitro Antioxidant activity [66]
DPPH (%) FRAP (μg AAE/g) Ferrous Ion chelating (%)
Fruit (Aqueous) 1.356 0.050 59.94
Fruit (Methanolic) 2.256 0.026 59.62
Fruit (Ethanolic) 3.872 0.027 61.75
In-vitro Antioxidant activity [73]
DPPH (μmol/lit) FRAP (IC 50)
Wild Leaves 437 14.65
Cultivated Leaves 620 11.80
In-vitro Antioxidant activity (%) [33]
DPPH Reducing power
Leaves (Aqueous) 81.25 0.062
Leaves (Ethanolic) 80.14 0.292
Leaves (Methanolic) 79.11 0.272
In-vitro Antioxidant activity (%)
DPPH ABTS Phosphomolybdenum reduction Ferric reducing power [237]
Pulp (Aqueous) 60.70 95.77 87.81 52.05
In-vitro Antioxidant activity (%)
DPPH Phosphomolybdenum reduction Ferric reducing power [240]
Fruit (Ethanolic) 93.67 67.83 81.70
Fruit (Aqueous) 68.20 57.14 66.92
Fruit (Ethyl acetate) 43.27 42.83 61.90
Fruit (Hexane) 33.40 34.56 34.35
Fruit (Methanolic) 54.41 55.32 74.32
T. Sarkar et al. Journal of Agriculture and Food Research 2 (2020) 100081
16

17. experiment with bael essential oil in Wistar rats, it is found that tri-
glyceride content has decreased and urea content change without
affecting creatinine proves the nontoxic behaviour of bael [205]. Any
abnormalities have not been observed in pregnant rats with the admin-
istration of bael extract [206].
8.32. Anti-oxidant activity
Oxidative stress and nitrosative stress both can be a result of ROS and
reactive nitrogen species (RNS). Superoxide anion radical (O2), hy-
droxyl radical (OH), NO, peroxynitrite (ONOO) and hydrogen peroxide
(H2O2) can do severe damage to cells [155]. Different diseases particularly
cancer and cardiovascular diseases have been a result of the generation of
ROS. Various plants contain antioxidants or polyphenol compounds that
can be effective against ROS [120,207]. Different phytochemicals like
terpenoids, tannins, flavonoids, and steroids are responsible for antioxi-
dant activity in bael [7]. Different methods like 2, 2-diphenyl-1-picrylhy-
drazyl (DPPH) radical scavenging assay, ABTS radical scavenging assay,
and superoxide radical scavenging assay have been used to see the anti-
oxidant activity of methanolic and aqueous extract of bael. It is found that
unripe fruit can more effectively exhibit antioxidant activity than ripe
fruit. Chloroform and aqueous extract of bael can significantly show free
radical scavenging activity and also show inhibition against lipoxygenase
enzyme [147]. From Pearson's correlation, it is observed that bael pos-
sesses anti-oxidant activity due to phytochemicals such as phenolic acids
and flavonoids [180]. In another study, it is believed that phenol moiety is
highly reactive, and different mechanisms are followed for antioxidant
activity but specifically radical scavenging following hydrogen ion dona-
tion is the principal method. The aromatic ring of phenolic acid contains
different substituents and depending on that different phenolic acids
exhibit different antioxidant activity [208]. Arabinogalactan protein
(AGP) present in fruit gum with which β-lactoglobulin forms a water
complex. The study finds that AGP may be comparable to standard
anti-oxidants [209]. Sprague-Dawley rat gastric system shows the meth-
anolic extract of unripe bael can effectively inhibit the fall in enzymatic
and non-enzymatic antioxidants [132]. Scavenging activity of hydro-
alcoholic extract of bael shows radical scavenging activity against DPPH
and 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulphonic acid) radicals. 2,
2'-azobis (2-amidinopropane) dihydrochloride radical-promoted oxidation
seen in biomolecules like plasmid DNA, bovine serum albumin, and lipids
can be halted with the use of bael extract [210]. Umbelliferone, β-D-ga-
lactopyranoside present in the stem bark of bael helps in boosting gluta-
thione peroxidase (GPx), SOD, and CAT [1]. A study proves that the
ethanolic extract of bael leaf may be effective against MDA formation in
linseed oil [211]. The in-vitro antioxidant activities of different parts of
bael are represented in Table 5.
9. Other uses of bael
The unripe seed contains gum which may be used as adhesive for
jewellery, lime plaster or cement can be mixed with, for waterproofing or
plastering walls. For textile prints, dyeing of silk fabrics the yellow dye
obtained from tannin can be used. Mermelle oil has been used by the
Dutch of Ceylon. Bael could be used in preventing scum formation and
preparing carts. Tool and knife handle, small-scale turnery, pestles, and
combs are prepared from it. Insecticidal activity is found against brown
planthopper [212]. Methanolic bael extract shows anti-parasitic activity
against Haemaphysalis bispinosa [82]. Activated carbon from the bael fruit
shell may act as an adsorbent to remove Chromium (VI) toxic metal from
the aqueous system [213]. Lead (II) can be removed when present with
other metals from exhausted batteries by the use of bael [214].
10. Conclusion
Highly promising therapeutic activities have been acquired by bael
and thus worthy of detailed investigation. Exploring the phytochemistry
of fruit cast light on enormous phytochemicals especially alkaloids,
coumarins, essential oils, phenols, flavonoids, and their extraordinary
power as a natural magical remedy to various diseases. Clinical trials
have declared the non-toxic behaviour of bael which ensures the phar-
macological application is extremely safe without any side effects.
Furthermore, the cultivation of the plant is absolutely simple and re-
quires no special care which enlightens the economic aspect of the use of
the fruit. Therefore farmers should be motivated for the cultivation of
this plant. To date, numerous studies have focused on the presence of
bioactive compounds in bael but most of their mechanism of action at the
molecular level is still unknown. Apart from the consumption of fresh
juice focus must be given to storing the fruit by preparing alternate
products and export them. Though the traditional medicine system has
immensely practiced bael from ancient times it is high time to find out
more information on the mode of action of bioactive compounds in the
fruit and make it popular worldwide in terms of consumption to enjoy the
exceptional health benefits.
Declaration of competing interest
The authors declare no conflict of interest.
Acknowledgment
The authors are grateful to the Editor-in-Chief of this journal, Dr.
Yangchao Luo from the Department of Nutritional Sciences at the Uni-
versity of Connecticut (Storrs, Connecticut, United States), for his thor-
ough guidance and sharing his immense experience on improving the
quality of the work.
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