Phytochemical and Biological Review of Aegle Marmelos Linn

Abstract

India has one of the most expanded plant-origin medical traditions in the world. Researchers have evaluated molecules obtained from plants to treat a variety of ailments. Literature review shows that fundamental parts of the plant are used to treat different diseases. The related data is retrieved from Google scholar, PubMed, Science Direct and Scopus. The keywords include Bael, A. marmelos, Vilvam, and Marmelosin. Extensive studies show that A. marmelos has antidiarrhoeal, antimicrobial, antiviral, anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility, and anti-inflammatory properties. In this work, an updated literature review is presented to clarify the current state of research on A. marmelos elucidating its constituents and their most relevant biological activities.

Full text

Review
For reprint orders, please contact: reprints@future-science.com
Phytochemical and biological review of
Aegle marmelos Linn
S Monika1, M Thirumal*,1 & PR Kumar1
1Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science & Technology, Kattankulathur, Chengalpet
Dt, Tamilnadu, 603203, India
*Author for correspondence: Tel.: +91 98946 40595; thirumam@srmist.edu.in
India has one of the most expanded plant-origin medical traditions in the world. Researchers have
evaluated molecules obtained from plants to treat a variety of ailments. Literature review shows that
fundamental parts of the plant are used to treat different diseases. The related data is retrieved from
Google scholar, PubMed, Science Direct and Scopus. The keywords include Bael, A. marmelos, Vilvam,
and Marmelosin. Extensive studies show that A. marmelos has antidiarrhoeal, antimicrobial, antiviral,
anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility, and anti-
inammatory properties. In this work, an updated literature review is presented to clarify the current
state of research on A. marmelos elucidating its constituents and their most relevant biological activities.
Plain language summary: India has one of the most expanded plant-origin medical traditions in the world.
A. marmelos Linn, also familiar as bael, belongs to Rutaceae and is widely grown worldwide. A. marmelos
is a fruit with various medicinal advantages. We searched various databases, studied elaborately, and
understood the importance of this fruit. Thus, its constituents can help mitigate various diseases.
Graphical abstract:
O
O
H
3
C
CH
3
O
O
H
3
C
HO
CH
2
O
OH
HO
HO
CH
3
OO
HO OH
O
HO OH
O
O
OH
OH
H
3
C CH
3
CH
3
O O O
O
CH
3
N
O
H
3
C
O
CH
3
CH
2
H
3
C
Phytochemistry and biological activities of Aegle marmelos Linn
Flavone (antidiabetic)
Cumin aldehyde (lnsecticidal)
Eugenol (antibacterial)
Rutin (antioxidant)
Auraptene (anticancer)
Fagarine (antimalarial)
D-limonene (antiulcer)
First draft submitted: 25 October 2022; Accepted for publication: 2 March 2023; Published online:
23 March 2023
Keywords: Aegle marmelos •Marmelosin •phytochemistry •Rutaceae •Vilvam
Future S ci. OA (2023) FSO849 eISSN 2056-562310.2144/fsoa-2022-0068 C
2023 The Authors

Review Monika, Thirumal & Kumar
The medicinal plant performs an essential role in the lives of underprivileged populations worldwide [1], likewise
for primary medical care. Approximately 80 percent of countries worldwide rely on these conventional treatments,
which frequently involve plant extracts [2]. India has one of the most expanded plant-origin medical traditions in
the world. In India, rural communities know around 25,000 potent plant-based remedies employed in traditional
medicine. Plants, especially those with ethno pharmacological uses, have been the primary sources of medicine for
early drug discovery [3]. Anciently most medications have been developed via natural ingredients or ingredients
derived from natural compounds [4,5].
However, a significant amount of basic and applied research is required to validate and use plants in phytophar-
maceutical chemistry, and the potential use of higher plants as a source of new medications is still underutilized,
with this resource ranking on par with conventional pharmaceutical products in terms of importance [6].Onlya
small portion of the approximated 250,000–500,000 plant genera have been thoroughly explored in terms of their
pharmacological qualities, and only a small portion have been investigated phytochemically [7].Bysupportingthe
conscious exploration of biodiversity as a source of bioactive molecules and their application in the production
of new therapeutic medications, it also aims to encourage the developing and disseminating of this plant-based
medicine. The main aim of this review is to know the phytochemical parameters, Traditional uses, and innovative
applications of A. marmelos Linn.
Research method
The search is done in Google scholar, PubMed, Science Direct and Web of Science. The databases are collected by
the following keywords: Bael, A. marmelos, Vilvam, and Marmelosin.
Inclusion & exclusion criteria
The language of this study is English. It included chemical, and pharmacological data and specific animal trials using
isolated chemicals and extracts from A. marmelos. Finally, to ensure dependability, only peer-reviewed academic
publications are selected. This study excluded the clinical trials and computational and characterization studies.
350 articles were selected; from that, 79 articles were included.
Rutaceae family
The most recent phylogeny for Rutaceae, with 135 genera representing 87.7% of the recognized genera for Rutaceae
and subfamilies of the family are Haplophylloideae, Amyridoideae, Aurantioideae, Cneoroideae, Rutoideae, and
Zanthoxyloideae. The physiologically active essential oils produced by the Rutaceae family are widely known and
found in many family members, as well as its ornamental and culinary herbs, which include orange, lime, lemon,
grapes, and satinwood [8]. Several studies have found various plant substances, including alkaloids, terpenoids,
flavonoids and coumarins [9]. Plants in the Rutaceae family contain high amounts of coumarins, like Marmelosin
and Luvangetin, which have antihelminthic, antiulcer, antibacterial and antispasmodic activity.
Aegle marmelos Linn
Aegle marmelos Linn, also familiar as Bael as shown in Figure 1 and belonging to the family Rutaceae, has been
frequently utilized in the indigenous Indian system of medicine because of its diverse medicinal properties. India
holds high regard for the critical medicinal herb A. marmelos Linn (Rutaceae), also called Bengal quince, Bilva,
Indian quince, Golden apple, Holy fruit, Bel, Belwa, Sriphal, Stone apple, and Maredo in India [10]. It has been
utilized for over 5000 years by numerous ethnic populations living in the Indian subcontinent. In the ayurveda
Indian traditional medicine system, it is used to treat various ailments [11]. The phytochemicals of A. marmelos were
discovered in various sections of the same plant.
Indian medicinal plant known as bael has been used traditionally to treat several ailments, and numerous bioactive
chemicals have been extracted [12,13].A. marmelos, native to Northern India, are also widely dispersed over the
Indian Peninsula, Burma, Bangladesh, Ceylon, Thailand and Indo–China [14]. The medium-sized, slow-growing
A. marmelos tree can grow to 12–15 meters. It spreads with spiky branches and has a small trunk and thick, soft,
peeling bark. Fractured branches, a transparent, viscous liquid that resembles gum arabic, oozes out, hangs down
in long strands, and gradually solidifies. It starts tasting sweet but soon becomes unpleasant to the throat [15,16].
The biologically active chemicals and essential oil were extracted from Bael plants, and phytoconstituents
characterization was carried out. Extraction techniques are used on the most active parts of the plant (roots,
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
Figure 1. Bael fruit and tree.
Table 1. Taxonomical classication .
Kingdom Plantae
Sub-kingdom Tracheobionta
Super division Spermatophyta
Division Magnoliophyta
Class Magnoliopsida
Subclass Rosidae
Order Sapindales
Family Rutaceae
Genus Aegle
Species marmelos
Table 2. Ethno medicinal uses of Aegle marmelos .
Parts Uses
Leaves The leaves are most effective in treating fever, nausea, vomiting, swellings, dysentery, dyspepsia, seminal weakness, and intermittent
fever.
Root The roots of bael are thought to be effective in treating urinary problems, preventing heart palpitations, and curing fevers. They are
also said to relieve abdominal pain. The medical properties of dashamula lie in its root to treat fever, diarrhea, and atulence.
Bark The villagers use a decoction of the bark to treat fever and cough.
Flower An anti-dysenteric, antidiabetic, diaphorectic, and local anesthetic medication can be produced by distilling owers. It is utilized as a
tonic for the stomach and intestine. Along with being used as an expectorant, it is also helpful in epilepsy.
Fruit Bael fruits are edible. The pulp used to make delicious items like murabba, puddings, and juice. Apart from their laxative use and
curing respiratory ailments, also used in several traditional medications to treat chronic diarrhea, peptic ulcers, inhibit lipid
peroxidation, free radicals scavenging, antioxidants, anti-ulcerative colitis, gastroprotective, hepatoprotective, antidiabetic,
cardioprotective, radioprotective, antibacterial, antidiarrheal and antiviral properties.
Seed Seed extract possesses antidiabetic and hypolipidemic effects in diabetic rats.
fruit, leaves, flowers, or stem), using selective solvents and standard operating procedures [17]. The taxonomical
classification of A. marmelos is discussed in Table 1 [18].
In traditional medicine, A. marmelos are used based on their radio protective [19], antidiabetic, and anticancer
activities [20,21]. The various components of bael are used for its medicinal properties, such as managing asthma,
fractures, anemia, wound healing, high blood pressure, jaundice, swollen joints, diarrhoea, and issues with typhoid
during pregnancy [22]. The medicinal importance of A. marmelos has been discussed in Table 2 [23–28] focusing on
each part of the plant.
A. marmelos is reported to contain chemical composition like alkaloids (aegeline, fragrine, aegelenine), coumarins
(Marmin, Marmelide, Psoralen, Imperatonin), and terpenoids (cineol, Caryophyllene), etc [29–36].
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
Table 3. Compound isolated from various parts of Aegle marmelos.
S. no Parts Chemical compound Ref.
i) Leaves ␣and ␤sitosterol, Rutin, Flavone, Cineol Glycoside, O- Halfordiol, Marmeline, Lupeol, Citronellal, Marmesinin,
Aeglin, Cuminaldehyde, Phenylethyl cinnamamides, Citral, Skimmianine, Eugenol, Isopentenyl.
[44]
ii) Fruit Aurapten, Imperatorin, Psoralen, Tannin, Luvangetin [45]
iii) Bark Fagarine, Marmin [37]
iv) Seed Citral, A-D-phellandrene, Cineol, P-cymene, D-limonene, Cumin aldehyde, Citronellal [46]
Reported phytochemical & its activity
The pulp of the bael fruit is rich in bioactive substances such as carotenoids, phenolics, alkaloids, pectins, tannins,
coumarins, flavonoids, and terpenoids, according to studies. Methanol and water are the best solvents for extracting
the metabolites of this plant, followed by ethanol [37–40]. The phytochemistry of A. marmelos has been extensively
studied, and the plant has been found to contain a variety of biologically active compounds.
Some of the key phytochemicals found in A. marmelos include: Alkaloids are nitrogen-containing compounds
that are found in many plants and are known for their pharmacological activity. Several alkaloids have been identified
in the leaves and roots of A. marmelos, including marmesin, marmelosin, and aegeline [25].
Tannins are a group of compounds that are widely distributed in the plant kingdom and are known for their
astringent and antioxidant properties. The fruit of A. marmelos contains high levels of tannins, which have been
shown to have strong antioxidant and anti-inflammatory activities. Flavonoids are a group of compounds that are
widely distributed in the plant kingdom and are known for their anti-inflammatory, anti-cancer, and antioxidant
activities.
Flavonoids have been identified in the leaves and roots of A. marmelos, and some of these compounds have been
shown to have antinociceptive (pain-relieving) and antipyretic (fever-reducing) activities [41].
Terpenoids are a group of compounds that are widely distributed in the plant kingdom and are known for their
medicinal properties. Terpenoids have been identified in A. marmelos, and some of these compounds have been
shown to have antifungal and antibacterial activities.
Saponins are a group of compounds that are widely distributed in the plant kingdom and are known for their
foaming and emulsifying properties. Saponins have been identified in the fruit and leaves of A. marmelos, and some
of these compounds have been shown to have antinociceptive and anti-inflammatory activities [33].
Glycosides are a group of compounds that are widely distributed in the plant kingdom and are known for
their medicinal properties. Glycosides have been identified in the fruit and leaves of A. marmelos, and some of
these compounds have been shown to have antinociceptive and anti-inflammatory activities [42]. The most widely
investigated compounds from A. marmelos were determined by reviewing and evaluating the items from the obtained
bibliographic data. The isolated phytochemicals from different parts of A. marmelos are discussed in Table 3,and
the chemical structure of the compounds is shown in Table 4 [43].
Pharmacological activity
Pharmacological activity is essential in herbal plants. The various acts of A. marmelos, which have been reported
scientifically and investigated, have been illustrated in Figure 2.
Anticancer activity
The A. marmelos of methanol and acetone extract of cytotoxicity against HEp-2, MDA-MB-231, and Vero cells
were investigated. The IC50 for the methanol extract of A. marmelos was 47.08 g/ml, whereas the IC50 for the
acetone extract of A. marmelos was 79.62 g/ml, making HEp-2 cells more sensitive to it. Both extracts of A.
marmelos are toxic to cancer cells; however, Vero cells can survive 24 hours [47].
MTT assays on the human breast cancer cell line MCF-7 at various concentrations confirmed the in vitro
anticancer activity. The flavonoids in fruit extracts act as a potential reducing agent and are reasonable for forming
gold nanoparticles [48].
The aqueous fruit pulp extract from A. marmelos caused the most excellent MCF7 cell death at 100 g/ml and
the IC50 at 47.92 g/ml concentrations [49].
In an in-vivo study, Swiss albino mice with Ehrlich ascites carcinoma received an intraperitoneal injection of a
400 mg/kg hydroalcoholic extract of A. marmelos. That significantly increased median survival time up to 28 days
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
Table 4. Chemical structures of compounds present in Aegle marmelos.
S. no Compounds Molecular formula Molecular Structure Activity
1. Aegelin C25H22O11
OH
OH
OHHO
CH
3
O O O
HO
H
3
C
CH
3
OH
O
Antidiabetic
2. Auraptene C19H22O3
O OO
H
3
C CH
3
CH
3
Inhibition of heart rate
3. Cineol C10H18 O
CH
3
CH
3
CH
3
O
Expectorant, Disinfectant
4. Citral C10H16 O
H
3
C
CH
3
CH
3
O
antibacterial, antifungal,
and antiparasitic
5. Citronellal C10H18O
H
3
C
CH
3
CH
3
O
Anticancer, antiseptic
6. Cumin aldehyde C10H12 O
H
3
C
CH
3
O
Insecticide
7. D-limonene C10H16
H
3
C
CH
3
CH
2
Dissolve
cholesterol-containing
gallstones
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
Table 4. Chemical structures of compounds present in Aegle marmelos (cont.).
S. no Compounds Molecular formula Molecular Structure Activity
8. Eugenol C10H12O2
H
2
C
OH
O CH
3
antibacterial, analgesic,
and antioxidant
9. Fagarine C13 H11NO3
CH
3
N
O
O
O
H
3
C
Antiplasmoidal
10. Flavone C15H10 O2
O
O
antifungal
11 Imperatorin C16H14O4
CH
3
CH
3
O
OO
O
Antiviral
12. Luvangetin C15 H14O4
CH
3
CH
3
H
3
C
OOO
O
Antiulcer
13. Marmin C 19H24 O5
CH
3
CH
3
H
3
C
OH
HO
O O O
Antiulcer
14. P-cymene C12 H14
CH
3
CH
3
H
3
C
antiviral, antitumor,
antibacterial, and
antifungal.
15. Psoralen C22 H6O3
O
O
O
Cytotoxic, antispasmodic
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
Table 4. Chemical structures of compounds present in Aegle marmelos (cont.).
S. no Compounds Molecular formula Molecular Structure Activity
16. Rutin C2H30O16
O
HO
HO
HO CH
3
O
O
HO
HO OH
O
OO
HO
OH
HO OH
Antioxidant,
Anti-inammatory
17. Skimmianine C13 H14NO4
N
O
O
O
O
H
3
C
CH
3
CH
3
Sedative, anticonvulsive,
analgesic
18. ␤sitosterol C29H50 O
H
3
C
H
3
C
CH
3
CH
3
CH
3
CH
3
HO
Antioxidant
45%
20%
4%
24%
7%
5%
15%
6%
Anti-cancer
Anti-ulcer
Anti-malaria
Anti-inammatory
Anti-diarrheal
Anti-diabetic
Anti-microbial
Anti-fertility
Figure 2. Percentage of reported biological activity of Aegle marmelos linked with each compound, from all
investigated articles.
after tumor inoculation compared with the saline-injected control group [21].TheA. marmelos fruit pulp’s ethanolic
extract has anti-proliferative effect by inhibiting the proliferation of breast cancers in a rat model. Both the breast
tumour volume (p <0.05) and the different blood biomarkers (p <0.0001) significantly decreased after A.
marmelos treatment [50].
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
Table 5. Antidiabetic activities of Aegle marmelos.
Part Extract Animal used Standard Inference
Fruit Aqueous Mice Glibenclamide lowers blood sugar and boosts insulin secretion
Fruit Lectin Glucose uptake by yeast cells Metformin IC50 of 3.36 μg/ml had greater efciency than the
usual medication
Various parts Petroleum ether, methanol,
chloroform, Benzene, aqueous
Streptozotocin diabetic Rabbit – Methanol extract showed maximum antidiabetic
effect
Seed Aqueous Albino Wistar rats Tolbutamide reduces the blood glucose level
Leaves Ethanol ␣-amylase and ␣-glycosidase
HepG2 cells
Acarbose ␣-amylase and ␣-glucosidase were found to be
IC50 123.65 μg/ml and IC50 141.56 μg/ml.
Reduced ROS levels and enhanced glucose
consumption (p ⬍0.05).
Leaves Chloroform, butanol, and water Streptozotocin induced Male
albino rats
Metformin Lowering the blood glucose levels
Antidiabetic activity
The aqueous extract of A. marmelos fruits lowers blood sugar in streptozotocin-induced diabetes rat model. It boosts
insulin secretion by partial regeneration from the β-cells of pancreatic islets [51]. The effects seen in the fruit extract-
treated mice were better when compared with animals treated with glibenclamide. The present study’s in-vitro
assay demonstrated a potent antidiabetic effect from lectin extract, as measured by glucose uptake in yeast cells [52].
A fruit lectin extract with an IC50 of 3.36 μg/ml had greater efficiency than the usual medication metformin at
increasing glucose uptake by yeast cells. This study found that A. marmelos fruit extract had hypoglycemic activity,
which could be attributed to its antioxidant activity and high content of active constituents [53].Asaresult,the
various parts of A. marmelos plant could be beneficial as a portion of healthy food and in developing antidiabetic
drugs. The active components in the leaf and callus materials reduce blood sugar levels in STZ-diabetic rabbits,
and A. marmelos callus powder methanol extract is as powerful as the leaf extract in treating diabetes, as discussed in
Table 5 [54]. This study indicates the aqueous seed extract of A. marmelos reduces the blood glucose level in normal
as well as in severely diabetic rats and improves glucose tolerance in sub and mild diabetic animals and is referred
to standard as tolbutamide [26]. The alcoholic extract of A. marmelos leaves significantly inhibited the enzymes
α-amylase and α-glycosidase with IC50 values of 46.21 and 42.07 μg/ml, respectively. A. marmelos significantly
reduced ROS levels that were elevated due to high glucose and enhanced glucose consumption in HepG2 cells
(p <0.05) [9].
Anti-inammatory & antipyretic activity
The study examined the potential anti-inflammatory activities of the repeated extracts from A. marmelos leaves. An
apparent analgesic effect was demonstrated in mouse models of carrageenan-induced paw edema and cotton-pellet
granuloma to establish the antipyretic and analgesic activities of the leaf extracts. Additionally, the early and late
phases of paw licking were diminished, and hyperpyrexia decreased [55]. In another study, the anti-inflammatory
properties of the aqueous extract of A. marmelos dried flowers are investigated in Wistar rats. The anti-inflammatory
effects of water extract were most effective at 200 mg/kg two hours after administration [56]. Aqueous extract from
unripe A. marmelos fruit was found to have a dose-dependent impact in a different investigation focused on
inflammatory bowel disease in albino Wistar rats. With much higher SOD and lower MDA levels and defense
against mast cell degranulation, A. marmelos fruit had anti-inflammatory, antioxidant, and mast cell stabilizing
properties [57].
Antimalarial activity
In vitro antimalarial activity of A. marmelos leaf methanol extract, which showed the highest activity against
Plasmodium falciparum, elicited low cytotoxicity, and the promising antiplasmodial activity of A. marmelos of IC50
is found to be 7 g/ml [58]. Infected mice with a suppressive effect on the parasite did not respond to C. longa
treatment; however, A. marmelos at 20 and 40 mg/kg body weight inhibited parasite infection. Finally, A. marmelos,
demonstrated strong antioxidant and antiplasmodial properties; it could be one of the traditional plants used to
treat malaria [59].WithanIC
50 of 500.06 ppm, standard Temephos has better larvicidal activity toward Anopheles
stephensi when compared with crude leaf extracts of A. marmelos Correa [60].
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
Table 6. Antimicrobial activity of Aegle marmelos.
Plant part Extract Method Organism Standard
Leaves Ethyl acetate Disc-diffusion method E. coli,S. typhii, and P.
aeroginosa
Streptomycin
Fruit pulp Aqueous, Ethanolic, and
petroleum
Standard tube dilution
technique
Staphylococcus aureus Ampicillin
Leaves Pet ether Disc-diffusion method Multi-resistant strains of
bacteria
Streptomycin
Antimicrobial activity
The antimicrobial activity of A. marmelos is discussed briefly in Table 6 respectively. Candida albicans, Aspergillus
niger, Aspergillus fumigatus,andStaphylococcus aureus all had MIC (Minimum inhibitory concentrations) values
of 19.5 g/ml, 39 g/ml, 625 g/ml, and 1.25 g/ml, respectively [61]. When used against Candida albicans and
Aspergillus niger, it showed practical MFC (Minimum fungicidal Concentration) values of 2.5 mg ml-1 and5mg
ml-1, respectively. In the present review, the decoction was more effective against fungi than food-pathogen bacteria.
The control drug ampicillin was identified to be effective as similar to the ethanolic extract of A. marmelos fruit
pulp by inhibiting the growth of pathogenic bacterial strains [62]. The antibacterial activity of the different A.
marmelos leaf extracts was tested using the disc diffusion method on multi-resistant strains of bacteria. From there,
it can be shown that the pet ether extract exhibits greater action than regular streptomycin [63]. In the ethyl acetate
extract of A. marmelos leaf, the quinine compound was identified and possessed good antibacterial activity against
gram-positive and negative bacteria [64].
Antioxidant activity
Antioxidants are organic complexes that can safely interplay with free radicals and stop the chain reaction before
harming fundamental molecules. Free radicals are highly reactive molecular species containing one or more un-
paired electrons. They are generated from regular metabolism while using O2to burn food for energy [65].Itis
generally known that reactive oxygen species (ROS) play a role in developing several illnesses, including cancer and
cardiovascular disease. Plants include antioxidants or polyphenols that can successfully neutralize these ROS and
prevent the spread of disease [66]. Oxidative stress is produced during normal metabolic processes in the body and
induced by various environmental and chemical factors, which causes the generation of various reactive free radicals
and subsequent damage to macromolecules like DNA, proteins, and lipids. In comparison to standard - gallic acid
(IC50 1.1 ±0.08 μM), marmelosin exhibited potent antioxidant activity with an IC50 of ∼15.4 ±0.32 μMin
ethyl acetate extract of bael fruit. Marmelosin was discovered to have better antioxidant properties than standard
gallic acid [67]. In this investigation, the A. marmelos fruit decoction showed good antioxidant activity with an IC50
of 17.37 ±2.71 mg/ml and 379.9 ±28.28 mg AEAC/100 g for standard ascorbic acid [61].
Antispermatogenic activity
In A. marmelos bark extract, marmin and fagarine are high, reducing male fertility [68]. The ethanolic extract of
A. marmelos bark on sperm motility was reported to have a beneficial effect on sperm locomotor activity. It has
also been reported that increasing the concentration of extracts reduces sperm motility. The alkaloids isolated from
A. marmelos leaf were significantly decreased the fertility in male albino rats in dose dependent manner [69].A.
marmelos extract is an excellent choice for male contraception, the extract has the ability to completely suppress
pregnancy and restore fertility rapidly after treatment cessation [68]. The male albino rats reproductive systems were
subjected to three various doses of a 50% ethanolic extract from A. marmelos leaves: 100, 200, and 300 mg\kg
1 day 1 for each rat for 60 days. All of the significant accessory sex organs shrunk after ingesting the extract [70].The
cauda epididymis of the treated animals produced considerably less sperm, both in terms of motility and density.
Male rat fecundity was completely decreased by A. marmelos at 300 mg.
Antiulcer activity
Methanolic and aqueous extracts of A. marmelos seeds were tested for antiulcer activity in indomethacin-induced
ulceration, stress-induced ulceration, and pylorus ligation-induced ulceration by using ranitidine as standard
(50 mg/kg) [71]. Peptic ulcers are caused by the bacteria H. pylori. There is little or no literature on the effect
of A. marmelos on Helicobacter pylori, so more research is required to determine its effect on H. pylori. If it
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
positively reduces AMR, it will be an excellent herbal drug to treat abscesses with no adverse effects [72].A. marmelos
is frequently used to heal ulcers and related illnesses in Ayurveda and observed for the oral administration of
methanolic extract of A. marmelos for affected rats with stomach ulcers induced by lipopolysaccharide caused by
Helicobacter pylori [73]. A dose of 500 mg/kg of methanolic extract was shown in the trial to reduce stomach ulcers
by 93.98%. Gastric secretory parameters, such as free and total acidity, acid output, stomach juice volume, and
pepsin concentration, were inhibited, resulting in decreased gastric ulcers.
Antiviral activity
Different portions of the A. marmelos are observed against human coxsackie viruses B1-B6 for in-vitro antiviral
activity with ribavirin as a standard antiviral drug. Thus Marmelide possessed 32-times more potent inhibitory
activity than ribavirin [74].A. marmelos extracts were shown to be effective against the white spot syndrome virus in
shrimp at a dose of 150 mg/kg of animal body weight [75]. The isolated volatile oil from A. marmelos is examined for
its ability to inhibit the growth of eight different types of fungi. At 0.05% concentration, the essential oil completely
prevented all fungi from producing spores. The majority of the fungus is significantly inhibited at around 75%
and 90% at 0.03% and 0.04%, respectively. At concentrations of 0.03% and 0.04% of the oil, the most resistant
strain, F.udum, showed 65% and 80% inhibition rates, respectively [76].
Toxicity studies
A. marmelos dried fruit pulp is examined for its topical characteristics. Swiss albino mice were tested for acute oral
toxicity with an ethanol extract of the dried fruit pulp from A. marmelos at 550 and 1250 mg/kg. Test results
should indicate that the extract is not hazardous at these doses. Mice’s behavior and physiological activity remained
unchanged (14 days) throughout the trial [43]. The findings showed that the test extract’s LD50 is highly significant.
The oral acute toxicity study did not show any toxic symptoms, changes in behavior, or mortality at 1250 mg/kg
doses. Thus, the ethanolic extract of A. marmelos dried fruit pulp extract has no discernable biologically significant
toxic effect on the mice below LD50.
Discussion
The biological actions of isolated compounds from A. marmelos that are being investigated using extracts can
be connected to this review. This investigation concludes that A. marmelos has a promising future in treating
and preventing different ailments, including cancer, infectious disorders and diabetic conditions. Reviews on
spermatogenic, analgesic and antipyretic, inflammatory, antiulcer, and malaria treatment drugs are only a few
topics covered in these reviews. For this reason, it is essential to develop clinical research on this medicinal plant
and learn from traditional healers who have gathered knowledge through many generations of trial and error. The
use of bael has gained popularity worldwide as its beneficial characteristics are being researched to develop new
treatments potentially. As a result, the demand for novel therapeutic drugs with focused action and limited adverse
effects justifies further clinical and preclinical research on A. marmelos.
Conclusion
These investigations have shown that A. marmelos has therapeutic potential and contains elements that could be
used to make new medications for the prevention, mitigation, or treatment of diabetes, cancer, and a variety of
pathogenic illnesses. A. marmelos has been historically used for a variety of ethno botanical purposes. Unfortunately,
most compounds still need to be thoroughly assessed to investigate novel lead molecules or pharmacophores.
Furthermore, the mechanisms of a few bioactive chemicals have been discovered so far. Comprehensive research is
necessary to ascertain the mechanisms of action, the bioactivity of numerous phytochemicals, and the effectiveness
of A. marmelos medicinal characteristics.
Future perspective
This study concludes the various parts of A. marmelos; preclinical studies are performed for different activities. Many
chemical compounds are isolated, but fewer studies are conducted. In the future, clinical trials will be conducted
for those activities. The demand for Bael fruit is likely to increase due to its growing popularity as a health food
and ingredient in various food and beverage products. Additionally, the growing interest in traditional and natural
remedies for various health conditions is likely to drive demand for Bael fruit.
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
Executive summary
Rutaceae
•Aegle marmelos (Indian bael or bael fruit), Rutaceae family, tree species native to India and Southeast Asia.
Aegle marmelos Linn
•Traditionally used for the treatment of various ailments, including diarrhoea, dysentery, and fever.
Reported phytochemical & its activity
•Phytoconstituents, including alkaloids, coumarins, tannins, avonoids, terpenoids, saponins, and glycosides.
Pharmacological activity
•Antibacterial, antifungal, antiviral, antimalarial, and antiparasitic activities.
Author contributions
Literature research and writing have been done by S Monika and M Thirumal. Actualization has been done by PR Kumar. English
vocabulary as well as phrase structure revision of the whole document have been done by S Monika. M Thirumal was the supervisor
of all work.
Acknowledgments
The authors express sincere gratitude to all the supervisors and professors of SRM College of Pharmacy, SRM Institute of Science
and Technology, Kattankulathur (Tamil Nadu, India), who extended their contribution and support in this work.
Financial & competing interests disclosure
The authors have no relevant afliations or nancial involvement with any organization or entity with a nancial interest in or nan-
cial conict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Open access
This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit
http://creativecommons.org/licenses/by/4.0/
References
Papers of special note have been highlighted as: •of interest
1. Shinwari ZK, Qaiser M. Efforts on conservation and sustainable use of medicinal plants of Pakistan. Pak. J. Bot. 43(1), 5–10 (2011).
2. Li R-J, Gao C-Y, Guo C, Zhou M-M, Luo J, Kong L-Y. The anti-inflammatory activities of two major withanolides from Physalis
minima via acting on NF-κB, STAT3, and HO-1 in LPS-stimulated RAW264.7 cells. Inflammation 40(2), 401–413 (2017).
3. S¨
untar I. Importance of ethnopharmacological studies in drug discovery: role of medicinal plants. Phytochem. Rev. 19(5), 1199–1209
(2020).
•There is an reference addressing the drug discovery and drug development in traditional medicine.
4. Katiyar C, Kanjilal S, Gupta A, Katiyar S. Drug discovery from plant sources: an integrated approach. AYU (An Int. Q. J. Res. Ayurveda)
33(1), 10 (2012).
5. Lahlou M. The success of natural products in drug discovery. Pharmacol. Pharm. 4(3A), 15 (2013).
6. Vuorela P, Leinonen M, Saikku P et al. Natural Products in the Process of Finding New Drug Candidates. Curr.Med.Chem.11(11),
1375–1389 (2004).
7. Rates SM. Plants as source of drugs. Tox i c o n 39(5), 603–613 (2001).
8. Appelhans MS, Bayly MJ, Heslewood MM, et al. A new subfamily classification of the Citrus family (Rutaceae) based on six nuclear and
plastid markers. Ta x o n 70(5), 1035–1061 (2021).
9. Ahmad W, Amir M, Ahmad A et al. Aegle marmelos leaf extract phytochemical analysis, cytotoxicity, in vitro antioxidant and antidiabetic
activities. Plants 10(12), 2573 (2021).
10. Vinita Bisht N, Johar V. Bael (Aegle marmelos) extraordinary species of India: a Review. Int.J.Curr.Microbiol.Appl.Sci.6(3),
1870–1887 (2017).
11. Rahman S, Parvin R. Therapeutic potential of Aegle marmelos (L.)-An overview. Asian Pacific J. Trop. Dis. 4(1), 71–77 (2014).
12. Badam L, Bedekar S, Sonavane KB, Joshi SP. In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses
B1-B6. J. commun. Dis. 34(2), 88 (2002).
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
13. Gupta AK, Tandon N. Reviews on Indian medicinal plants. Indian Council of Medical Research, New Delhi, India 1, 312 (2004).
14. Brijesh S, Daswani P, Tetali P, Antia N, Birdi T. Studies on the antidiarrhoeal activity of Aegle marmelos unripe fruit: validating its
traditional usage. BMC Complement. Altern. Med. 9, 47 (2009).
15. Kaur A, Kalia M. Physico chemical analysis of bael (Aegle marmelos) fruit pulp, seed and pericarp. Chem. Sci. Rev. Lett. 6(22), 1213–1218
(2017).
16. Aung HT, Zar T, Sein MM, Komori Y, Vidari G, Takaya Y. Constituents of Aegle marmelos from Myanmar. J. Asian Nat. Prod. Res.
23(9), 844–850 (2021).
17. Badal S, Delgoda R. Pharmacognosy fundamentals, applications and statergy. Academic Press, London, UK (2016).
18. Boy HIA, Rutilla AJH, Santos KA et al. Recommended medicinal plants as source of natural products: a Review. Digit. Chinese Med.
1(2), 131–142 (2018).
19. Jagetia GC, Venkatesh P. Inhibition of radiation-induced clastogenicity by Aegle marmelos (L.) Correa in mice bone marrow exposed to
different doses of γ-radiation. Hum. Exp. Toxicol. 26(2), 111–124 (2007).
20. Subramaniam D, Giridharan P, Murmu N et al. Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde,
a Novel Compound from Aegle marmelos.Cancer Res. 68(20), 8573–8581 (2008).
21. Jagetia GC, Venkatesh P, Baliga MS. Aegle marmelos (L.) Correa. Inhibits the Proliferation of Transplanted Ehrlich Ascites Carcinoma in
Mice. Biol. Pharm. Bull. 28(1), 5864 (2005).
22. Sanghi SB, Mushtaq S. Aegle marmelos a potential medicinal tree: an overview. Int. J. Res. -Granthaalayah 5(8), 63–66 (2017).
23. Mazumder R, Bhattacharya S, Mazumder A, Pattnaik AK, Tiwary PM, Chaudhary S. Antidiarrhoeal evaluation of Aegle marmelos
(Correa) Linn. root extract. Phyther. Res. 20(1), 82–84 (2006).
24. Soumya Prakash Rout, Choudary KA, Kar DM, Das L, Jain A. Plants in traditional medicinal system - future source of new drugs.
International J. Pharm. Pharm. Sci. 1(1), 1–23 (2009).
25. Baliga MS, Bhat HP, Joseph N, Fazal F. Phytochemistry and medicinal uses of the bael fruit (Aegle marmelos Correa): a concise review.
Food Res. Int. 44(7), 1768–1775 (2011).
26. Kesari AN, Gupta RK, Singh SK, Diwakar S, Watal G. Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in
normal and diabetic rats. J. Ethnopharmacol. 107(3), 374–379 (2006).
27. Nemkul CM, Bajracharya GB, Shrestha I. Phytochemical, antibacterial and DPPH free radical scavenging evaluations of the barks of
Aegle marmelos(L.) Correa. J. Pharmacogn. Phytochem. 7(4), 1637–1641 (2018).
28. Dhankhar S, Ruhil S, Balhara M, Dhankhar S, Chhillar AK. Aegle marmelos (Linn.) Correa: a potential source of Phytomedicine. J. Med.
Plants Res. 5(9), 1497–1507 (2011).
29. Ali MS, Pervez MK. Marmenol: a 7-geranyloxycoumarin from the leaves of Aegle marmelos corr. Nat. Prod. Res. 18(2), 141–146 (2004).
30. Takase H, Yamamoto K, Hirano H, Saito Y, Yamashita A. Pharmacological Profile of Gastric Mucosal Protection by Marmin and
Nobiletin from a Traditional Herbal Medicine, Aurantii fructus immaturus.Jpn J. Pharmacol. 66(1), 139–148 (1994).
31. Sharma B, Sharma P. Constituents of Aegle marmelos.Planta Med. 43(09), 102–103 (1981).
•Reference addressing the ethanobotanical uses of Aegle marmelos.
32. Gerardo Aguirre, Araceli Salgado-Rodr´
ıguez, Luc´
ıa Z Flores-L´
opez, MP-H y Ratnasamy Somanathan. Asymmetric Synthesis of
Naturally Occurring β-Hydroxyamides (R)-Tembamide and (R)-Aegeline. JMex.ChemSoc.45, 21–24 (2001).
33. Wilzer KA, Fronczek FR, Urbatsch LE, Fischer NH. Coumarins from Aster praealtus.Phytochemistry 28(6), 1729–1735 (1989).
34. Goel RK, Maiti RN, Manickam M, Ray AB. Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect
on prostanoid synthesis using human colonic mucosa. Indian J. Exp. Biol. 35(10), 1080–1083 (1997).
35. Masuda T, Takasugi M, Anetai M. Psoralen and other linear furanocoumarins as phytoalexins in Glehnia littoralis.Phytochemistry 47(1),
13–16 (1998).
36. Gautam M, Ramanathan M. Ameliorative potential of flavonoids of Aegle marmelos in vincristine-induced neuropathic pain and
associated excitotoxicity. Nutr. Neurosci. 24(4), 296–306 (2021).
37. Maity P, Hansda D, Bandyopadhyay U, Mishra D. Biological activities of crude extracts and chemical constituents of Bael, Aegle
marmelos (L.) Corr. Indian J. Exp. Biol. 47, 849–861 (2009).
38. Sharma GN, Dubey SK, Sati N, Sanadya J. Phytochemical screening and estimation of total phenolic content in Aegle marmelos seeds.
Int. J. Pharm. Clin. Res. 2(3), 27–29 (2011).
39. Veer B, Singh R. Phytochemical Screening and Antioxidant Activities of Aegle marmelos Leaves. Anal. Chem. Lett. 9(4), 478–485 (2019).
40. Venkatesan D, Karrunakarn CM, Kumar SS, Swamy P. Identification of phytochemical constituents of Aegle marmelos responsible for
antimicrobial activity against selected pathogenic organisms. Ethnobot. Leafl. 11(4), 1362–1372 (2009).
41. Choudhary Y, Saxena A, Kumar Y, Kumar S, Pratap V. Phytochemistry, pharmacological and traditional uses of Aegle marmelos.Pharm.
Biosci. Journal. 20, 27–33 (2017).
•There is an reference addressing phytochemical present in Aegle marmelos.
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group

Phytochemical & biological review of Aegle marmelos Linn Review
42. Dhankhar S, Ruhil S, Balhara M, Dhankhar S, Chhillar AK. Aegle marmelos (Linn.) Correa: a potential source of Phytomedicine. J. Med.
Plants Res. 5(9), 1497–1507 (2011).
43. Rakulini K. A Review of Anti-Diarrhoeal Activity of Aegle marmelos.J. Complement. Altern. Med. Res. 7(2), 1–10 (2019).
44. Shoeb A, Kapil RS, Popli SP. Coumarins and alkaloids of Aegle marmelos.Phytochemistry 12(8), 2071–2072 (1973).
45. Kim HJ, Seo YJ, Htwe KM, Yoon DK. Chemical Constituents from Aegle marmelos Fruit s. Nat. Prod. Sci. 27(4), 240–244 (2021).
46. Pathirana CK, Madhujith T, Eeswara J. Bael (Aegle marmelos L. Corrˆ
ea), a Medicinal Tree with Immense Economic Potentials. Adv.
Agric. 2020, 1–13 (2020).
47. Seemaisamy R, Faruck LH, Gattu S, et al. Anti Microbial and Anti Cancer activity of Aegle marmelos and Gas Chromatography Coupled
Spectrometry Analysis of their Chemical Constituents. Int. J. Pharm. Sci. Res. 10(1), 373–380 (2019).
48. Vijayakumar S. Eco-friendly synthesis of gold nanoparticles using fruit extracts and in vitro anticancer studies. J. Saudi Chem. Soc. 23(6),
753–761 (2019).
49. Vardhini SP, Sivaraj C, Arumugam P, Ranjan H, Kumaran T, Baskar M. Antioxidant, anticancer, antibacterial activities and GCMS
analysis of aqueous extract of pulps of Aegle marmelos (L.) Correa. J. Phytopharm. 7(1), 72–78 (2018).
50. Akhouri V, Kumari M, Kumar A. Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats. Sci.
reports. 10(1), 18016 (2020).
51. Kamalakkannan N, Prince PSM. The effect of Aegle marmelos fruit extract in streptozotocin diabetes: a histopathological study. J. Herb.
Pharmacother. 5(3), 87–96 (2005).
52. Saha RK, Nesa A, Nahar K, Akter M. Anti-diabetic Activities of the Fruit Aegle mamelos.J. Mol. Biomark. Diagn. 7(2), 1–5 (2016).
53. Abdallah IZA, Salem IS, Abd El-Salam NAS. Evaluation of Antidiabetic and Antioxidant Activity of Aegle marmelos L. Correa Fruit
Extract in the Diabetic Rats. Egypt. J. Hosp. Med. 67(2), 731–741 (2017).
54. Arumugam S, Kavimani S, Kadalmani B, Ahmed AB, Akbarsha MA, Rao MV. Antidiabetic activity of leaf and callus extracts of Aegle
marmelos in rabbit. ScienceAsia 34(3), 317–321 (2008).
55. Arul V, Miyazaki S, Dhananjayan R. Studies on the anti-inflammatory, antipyretic and analgesic properties of the leaves of Aegle
marmelos Corr. J. Ethnopharmacol. 96(1–2), 159–163 (2005).
56. Kumari KDKP, Weerakoon TCS, Handunnetti SM, Samarasinghe K, Suresh TS. Anti-inflammatory activity of dried flower extracts of
Aegle marmelos in Wistar rats. J. Ethnopharmacol. 151(3), 1202–1208 (2014).
57. Behera J, Mohanty B, Ramani Yr, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel
disease. Indian J. Pharmacol. 44(5), 614 (2012).
58. Kamaraj C, Kaushik NK, Rahuman AA, Mohanakrishnan D, Bagavan A, Elango G et al. Antimalarial activities of medicinal plants
traditionally used in the villages of Dharmapuri regions of South India. J. Ethnopharmacol. 141(3), 796–802 (2012).
59. Kettawan Aikkarach, Wongsansri Kanokkarn, Chompoopong Supin, Rungruang T. Antioxidant and antiplasmodial activities of
Curcuma longa and Aegle marmelos on malaria infeced mice (in vitro and in vivo). Siriraj Med. J. 64, 78–81 (2012).
60. Angajala G, Pavan P, Subashini R. One-step biofabrication of copper nanoparticles from Aegle marmelos Correa aqueous leaf extract and
evaluation of its anti-inflammatory and mosquito larvicidal efficacy. RSC Adv. 4(93), 51459–51470 (2014).
61. Gheisari HR, Amiri F, Zolghadri Y. Antioxidant and antimicrobial activity of Iranian Bael (Aegle marmelos) fruit against some food
pathogens. Int. J. Curr. Pharm. Res. 3(3), 85–88 (2011).
62. Behera P, Raj VJ, Basavaraju R. Phytochemical and antimicrobial activity of fruit pulp of Aegle marmelos.J. Chem. Pharm. Res. 6(8),
319–326 (2014).
63. Gavimath CC, Ramachandra YL, Rai SP, Sudeep HV, Ganapathy PS, Kavitha BT. Antibacterial activity of Aegle marmelos Correa leaves
extract. Asian J. Bio Sci. 3(2), 333–336 (2008).
64. Rejiniemon TS, Arasu MV, Duraipandiyan V, et al. In-vitro antimicrobial, antibiofilm, cytotoxic, antifeedant and larvicidal properties of
novel quinone isolated from Aegle marmelos(Linn.) Correa. Ann. Clin. Microbiol. Antimicrob. 13(1), 1–9 (2014).
65. Shrivastava V, Roy A. In vitro Antioxidant activity and phytochemical screening of Aegle marmelos extracts. Res. J. Pharmacogn.
Phytochem. 4(2), 80 (2012).
66. Panth N, Paudel KR, Parajuli K. Reactive Oxygen Species: A Key Hallmark of Cardiovascular Disease. Adv. Med. 2016, 1–12 (2016).
67. Pynam H, Dharmesh SM. Antioxidant and anti-inflammatory properties of marmelosin from Bael (Aegle marmelos L.); Inhibition of
TNF-αmediated inflammatory/tumor markers. Biomed. Pharmacother. 106, 98–108 (2018).
68. Srivastava AK, Singh VK. Anti-Fertility Role of Aegle marmelos (Bael). J. Appl. Heal. Sci. Med. 2(2), 21–25 (2022).
•There is an reference addressing the spermatogenic activity.
69. Kumar BS, Rao KM, Madhusudhan K, Reddy MK, Prasad MK. Isolation and evaluation of antifertility activity of total alkaloids from
leaves of Aegle marmelos in male albino rats (rattus norvegicus). International Journal of Applied Biology and Pharmaceutical Technology
2(3), 178–183 (2011).
future science group 10.2144/fsoa-2022-0068

Review Monika, Thirumal & Kumar
70. Chauhan A, Agarwal M, Kushwaha S, Mutreja A. Suppression of fertility in male albino rats following the administration of 50%
ethanolic extract of Aegle marmelos.Contraception 76(6), 474–481 (2007).
71. Sharma GN, Dubey SK, Sati N, Sanadya J. Ulcer healing potential of Aegle marmelos fruit seed. Asian J Pharm Life Sci. 1(2), 172–178
(2011).
72. Kumar TM. Exploring antibacterial & antiulcer activity of Aegle marmelos linn: a review. Int. J. Pharm. Chem. Anal. 7(3), 107–112
(2020).
73. Ramakrishna YG, Savithri K, Kist M, Devaraj SN. Aegle marmelos fruit extract attenuates Helicobacter pylori Lipopolysaccharide
induced oxidative stress in Sprague Dawley rats. BMC Complement. Altern. Med. 15, 375 (2015).
74. Badam L, Bedekar SS, Sonawane KB, Joshi SP. In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses
B1-B6. J. Commun. Dis. 34(2), 88–99 (2002).
75. Balasubramanian G, Sarathi M, Kumar SR, Hameed ASS. Screening the antiviral activity of Indian medicinal plants against white spot
syndrome virus in shrimp. Aquaculture 263(1–4), 15–19 (2007).
76. Rana BK, Singh UP, Taneja V. Antifungal activity and kinetics of inhibition by essential oil isolated from leaves of Aegle marmelos.J.
Ethnopharmacol. 57(1), 29–34 (1997).
10.2144/fsoa-2022-0068 Future S ci. OA (2023) FSO849 future science group