Medicinal Uses with Immense Economic Potential and Nutritional Properties of Aegle marmelos: A Concise Review

Abstract

Aegle marmelos is the only member of the monotype genus Aegle and belongs to the Rutaceae family, the citrus fruits family. This review shows the economically feasible pharmacological applications and the nutritional properties of A. marmelos. Each part of the A. marmelos/Bael tree such as root, bark, leaf, flower, fruit, and seed has therapeutic significance in Ayurvedic systems as well as other traditional medicines. In bael fruit, there are various valuable bioactive compounds that have remarkable nutritional and medicinal properties. The isolated components belong to alkaloids, terpenoids, vitamins, coumarins, tannins, carbohydrates, flavonoids, fatty acids, essential oils, and various other important biological agents. Various research studies have revealed the therapeutic effects that include antioxidant, antimicrobial, antibacterial, antidiarrheal, antiviral, antidiabetic, antiulcerative, and colitis nature of bael, which aids in inhibiting gastrointestinal problems, different cardiac issues, and other possible health benefit effects such as radioprotective effects, hepatoprotective effects, wound healing, peroxidation, inhibition of lipid, gastroprotective, cardioprotective, and free-radical scavenging (antioxidant) activity.

1. Introduction

Food is essential for life, and the main sources of food for animals especially for humans are different parts of the plant such as leaf, stem, fruits, seeds, flowers, and roots. Plants and their parts are not only used as a food but are also used as medicines. This is due to the presence of active chemical components in parts of the plant. Nowadays, various research and study applications have focused on the active chemical constituents of the plants and their functions due to the effectiveness, less side effects, synthesized easily, and most importantly economically feasible. Traditional uses of plants and plant parts also demonstrate the direction to use plants for the specific type of disease. A. marmelos (L.) Correa (Figure 1) is a very important indigenous plant to the Indian subcontinent for over 5000 years because of its economically feasible dietery and medicinal uses. The fruits of bael are of dietetic use, and the fruit pulp is used to make delights such as murabba, puddings, and juice. The subtropical fruit A. marmelos or commonly known as bael belongs to the Rutaceae family [1]. A. marmelos L., known by different names in different languages, such as Bel, Beli, and Belgiri in Hindi, Bilva, Shivadrums, Shivaphala, and Vilva in Sanskrit and Bael, Bengal quince, Indian quince, holy fruit, and golden apple in English and also known as Japanese bitter orange, stone apple, or wood apple (Table 1) [2]. In India, it is cultivated as a temple garden plant, and the leaves of A. marmelos are used to pray to Lord Shiva.

Figure 1.

Leaves and fruits of Aegle marmelos.

Languages	Different names of A. marmelos in corresponding languages
Hindi	Bel, Belgiri, Beli
Sanskrit	Bilva, Shivadrum, Vilva, Shivaphala
Telegu	Maredu
Kannada	Bilpatra, Malura, Kumbala,
Tamil	Kuvalum
Bengali	Bel
Gujrati	Bil
Cambodia	Phneou or Pnoi
Portugese	Marmelos
Java	Mojdo
French	Oranger du Malabar
Vietnamese	Bau Nau
Thai	Matum, Mapin

Table 1.

Various names of Aegle marmelos in different languages.

In different fields of science and technology, every part of this plant has a great utilization to cure many diseases. The variety of fruits is smaller in size than the other variety in the similar cultivated type [1]. Most common cultivar varieties of A. marmelos/Bael are Kagzi Gonda, Gonda no 1, Gonda no 2, Kagzi Etawah, Mirzapuri, and Baghel [1]. The potential effects of bael in different medicinal systems such as Ayurvedic, Unani, and Siddha have been already in use, and it states the functionality and feasibility of bael [3]. Many researches studies on bael approved that it consists of many nutritional elements such as a large group of phytochemicals, which includes alkaloids, flavonoids, tannins, phenolic acids, and coumarins. Except the above chemicals, other class of beneficial compounds such as amino acids, vitamins, a wide range of organic acids, carbohydrates, fatty acids, fibers, minerals make bael a highly nutritious fruit with immense health benefits, and the natural availability makes it economically feasible [4]. A. marmelos may cure gastrointestinal diseases such as diabetes, cardiac issues, and inflammation-related problems. It can acquire protective effects against the wound, microbes, radiation, free radical generation, and depression. The natural healing power of A. marmelos is proved by many research studies and applications [5]. A. marmelos fruit is a natural source of antioxidants and functional foods. It can be used in its dehydrated form such as jam, slab, bael powder, which makes it more useful for any kinds of season. A. marmelos and its various products and its various uses and applications make it extremely profitable, and the availability provides greater advantage over other similar kind [6, 7]. All seeds of A. marmelos are surrounded by gum having adhesive, waterproofing, and oil emulsion coating properties [8]. Due to the digestive and stomachic properties of bael, it is used in the treatment of diarrhea and dysentery [9]. It acquires tannins, reducing sugar, high amount of pectin, and very small amount of nonreducing sugar [10]. Due to presoluble and insoluble mucilaginous dietary fiber and pectin, it has great nutritional values. Many minerals and vitamins such as riboflavin, ascorbic acid, thiamine, niacin, vitamin A, calcium, and phosphorus are found in bael, which makes it healthy food [11]. Focus of this review is to highlight the composition of beneficial nutrients, formulation, and their medicinal uses with availability, quantification of phytochemicals, and economic view for production. This article will also be helpful for the industries for the production of medicines, bael products, food supplements and also helpful for researchers to make it more fruitful.

2. Botanical description

The growth of the A. marmelos tree is slow, and the height is nearly about 762 cm and 90–120 cm in girth [12], with a somewhat spiny branches of stem are observed in the bael tree [13]. Branches are armed with straight sharp axillary thrones, 2.5 cm long. Leaves alternate, 3 – foliate, rarely 5 – foliate; petiole 2.5–6.3 cm long, terete, 2.5 cm long. Leaflets 5–10 by 2.5–6.3 cm, ovate or ovate – lanceolates, crenate, acuminate, membranous, pellucid-punctate, the lateral opposite, subsessile, the terminal long petioluled. Table 2 shows the botanical classification of bael.

Kingdom	Plantae
Order	Sapindales
Family	Rutaceae
Subfamily	Aurantioideae
Genus	Aegle
Species	A. marmelos

Table 2.

Botanical classification of Aegle marmelos/bael.

The color of the leaves is different in different phase of the leaves; it is very green and fresh to see in the early stages, but later on it looks like dark green in color [13]. On observing the bark of the tree, it has been found that it is thick in nature, and after slightly thrashing the bark, then gum secretion is also observed, and it becomes thicker with the presence of air [13]. A. marmelos flower is hypogynous and bisexual in nature, and it smells sweet. The greenish-white bael flowers are collectively held by some lateral panicles, which are held by leaf axil [1, 14]. A. marmelos fruit has a hard, woody exocarp, and the fruit color 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% [15]. The color of the fruit pulp may vary from bright orange to sunset yellow, and the pulp contains seeds that are present in grooves and is surrounded by thick, clear mucilage. It contains some dots on the outer surface and also contains numerous seeds, which are hard and having thread-like hairs over their outer surface, which is white. The fruit is greenish when unripe, and upon ripening, it turns into yellowish color. Both ripe and unripe fruits are used for their medicinal values [16, 17].

3. Home remedy

Many home remedies are there, which are very useful for different diseases such as dysentery, diarrhea, digestion problem, etc. 1–3 drachms(drs) of the powder made from the mixture of A. marmelos fruit one part, Indian sweet fennel seeds one part, Holarrhena antidysentrica, two parts with Ispaghula, Sugar, Chebulic myrobalan, and plantago is very useful for chronic dysentery. There is another remedy that is very useful for both the chronic dysentery and diarrhea, and it can be prepared by mixing Andropogon muricatus one drop, Bael fruit four drops, Symplocos racemosa one drop, and Scindapsus officinalis one drop. In summer or very hot climate, another mixture of dried A. marmelos fruit pulp and Indian sweet fennel seeds both in a quantity of 21/2 drops with one drop gum of silk cotton tree, two drops honey, 1/2 drop dried ginger, and sugar is very useful in chronic diarrhea and dysentery [17].

4. Traditional uses

Extensive use of A. marmelos has been found in Ayurveda and traditional medicine system. In Ayurveda, the ripe fruit, which is acrid, bitter, and sweet, removes vatha and kapha, and it is good for the heart. Unani said that the ripe fruit is hot and dry; tonic, restorative, astringent, laxative; good for the heart and the brain; bad for the liver and chest [16, 18]. The unripe fruit is oily bitter, acrid, sour, tasty but difficult to digest, appetizer, binding cures dysentery, removes pain. The oil is hot and cures vatha. According to Siddha, A. marmelos has bitter, astringent taste, hot potency, pungent, bioavailability and reduces Vatha, Pitha, and Kapha dosha. The plant leaves can be used as an analgesic and antifungal agent [19]. Bael leaves are very useful for the treatment of asthma, hepatitis, hypogllcemia, and febrifuge. It has been also traditionally utilized for preparing medicinal mixes for numerous diseases or disorders. A. marmelos leaf powder may be used in the treatment of bowel syndrome [20]. It is used as a remedial measure in the treatment of beriberi [21]. A. marmelos leaf essential oil is reported to show various therapeutic actions [22]. The flower of A. marmelos has antiseptic properties and can be used as an astringent. In Thailand, the immature leaves and shoots of A. marmelos plant are consumed, whereas young leaves and shoots are consumed in Indonesia [23]. Flower is also used in epilepsy [24]. Marmala water, made from flower, is found helpful in catering conjunctivitis [25]. A. marmelos flower extract has been tested for wound-healing properties [24]. 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 [26]. The roots of A. marmelos have been used to cure dysentery, colitis, flatulence, and fever. So, in Chyavanprash, its roots are widely used [27]. In melancholia, heart palpitation, and intermittent fever, the decoction of root and bark is used [28, 29, 30]. Root bark may be used as a fish poison and fever treatment [31]. A. marmelos fruit extract is very helpful in thte treatment of thyroid. During pregnancy to prevent vomiting, it is found very helpful when it is taken with rice water in boiling conditions. In abscess curing, pulp powder of unripe fruit is very helpful to cure abscess [27]. On heating, sugar is produced from starch present in unripe fruit, 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 very helpful in the treatment of urinogenital disorders [7, 21]. A. marmelos fruits may be used as an antiscorbutic and stomatic agent, and it may cure diseases such as intestinal ulcer, gonorrhea, chronic constipation, and indigestion [21]. Mustard oil and powdered fruit in the ratio 2:1 are used in southern Chattisgarh in burn treatment [1]. Ripe fruit juice extract helps to cure chronic gastrointestinal disorder, piles treatment, and rectum inflammation, alongwith it reduces blood sugar levels owing to its bitter flavor [32, 33]. There is a great advantage of A. marmelos and its various parts that it can be preserved only by drying means; there are no chemicals are used alongwith and no costs are there to preserve for long time; really this advantage is profitable for the production of its processed food and medicines. In Thailand, it has been observed that dried A. marmelos leaf and fruit pulp are packed in tea bags and preserved in syrup for the further use in traditional preparation of desserts such as cake, juice, squash, nectar, jam, syrup, etc. [34]. A. marmelos plant acts as air purifier by absorbing harmful poisonous gas from atmosphere, making it inert/neutral and thus removing poisonous property. This is not only helps to reduce pollution, but also it clears the toxic effects and provides a fresh and healthy environment. As compared with other plants, A. marmelos can release higher amount of O₂ in the presence of sunlight, and plant is included in a category of “Fragrant” species because it can neutralize bad odors in air by deodorization process [32]. The unripe fruit yields yellow dye and is used for tanning calico and silk fabrics by textile industry [35]. This advantage is makes it more important and profitable for industry.

5. Nutritional properties

A. marmelos nutrients are extremely beneficial for being a healthy human, and this evidence is already proved by various research studies. Recent research studies not only focused on the nutritional benefits of A. marmelos but also focused on its low-cost production and marketing to build a healthy environment. Main composition of A. marmelos nutrients is water (60–65%), carbohydrate (9–21%), sugars (11–17%), fibers (5%), and other compositions are vitamins, minerals, glucose, various fatty acids, and amino acids [3, 36, 37]. Bael can prevents rancidity and color loss because it contains a valuable amount of vitamin A (55 mg), vitamin B and vitamin C (8 mg), which can act as an antioxidant [3, 38]. A. marmelos fruit pulp contains 1.7% mineral contents with copper (0.21 mg), potassium (610 mg), calcium (80 mg), phosphorous (52 mg), and iron (0.60 mg/100 g) [39]. The calorific value of A. marmelos (88 cal/100 g) is higher than that of apple (64 cal/100 g), guava (59 cal/100 g), and mango (36 cal/100 g) [40]. Like other fruits, A. marmelos is also providing different nutritional values in different stages of maturity. For estimating crude protein in dried fruits by Micro Kjeldahl’s distillation, to estimate crude fat Soxhelt method is used, ash content is estimated by incineration method [21, 41]. Xylose, threose, glucose, galactose, fructose, arabinose, sucrose, galacturonic acid are present in A. marmelos as a polysaccharides and as a fat present like ricinoleic, linolenic, oleic, linoleic, palmitic, and myristic [42]. The major and important parts of nutrients are found in seeds and leaf.

In A. marmelos seeds, there is present 34.4% oil, stearic acid 8.8%, linolenic acid 8.1%, palmitic acid 16.6%, and oleic acid 30.5% [43]. This seed oil is used in aromatherapy, cosmetics, and in compressor [44]. A. marmelos oil can be used in medical purposes such as an anti-inflammatory, antiseptic, antimicrobial, antioxidant, astringent, disinfectant, carminative, and cytophylactic.

6. Phytochemicals present in bael/Aegle marmelos

Flavonoids, carotenoids, phenolics, alkaloids, polysaccharides, terpenoids, phenylpropanoids, tannins, marmin, coumarin, etc., can found in A. marmelos (Figure 2) [45]. In leaves, the main constituents are cubebol 0.5%, γ-isogeraniol 0.2%, δ-cadinene 0.3%, γ-isogeraniol 0.2%, linalool 1.8%, menthane monoterpenoids 0.1%, α-terpineol 0.1%, α-cedrene 0.2%, germacrene B 4.7%, geraniol 0.2%, cis-piperitol 0.4%, Α-zingiberene 0.2%, γ-isogeraniol 0.2%, α-cubebene 0.1%, α-pinene 0.2%, α-humulene 0.8%, α-copaene 0.3%, myrcene 2%, γ-elemene 0.4%, limonene 64.1%, E-phytol 0.3%, γ-curcumene 1.7%, β-funebrene 0.2%, farnesol 0.1%, E-β-ocimene 9.7%, α-farnesene 0.1%, Z-jasmone 0.1%, E-caryophyllene 2.4%, germacrene A 0.1%, trans-Linalool oxide 0.1% [46].

Figure 2.

List of main bioactive compounds present in Aegle marmelos.

Many of the phytoconstituents having very good medicinal effects such as A. marmelos fruit pulp, fruit juice have been reported to be rich in numerous health-boosting polyphenols (Figure 2). Similarly, other health-benefited phytochemicals such as alkalloids, flavonoids, phenolic compounds, terpenoids have been accumulated in fruit pulp [47]. The most important polyphenols and flavonoids include alkaloids, coumarins, polysaccharides, and carotenoids. Polyphenols present in bael depend on the maturity stage of bael [48]. From showing antioxidant activities to lipid cholesterol absorption, these phytochemicals possess immense health benefits. Caffeic cinnamamides acid, arbutin, cholorogenic acid, p-coumaric acid, p-coumaroyl, quinic acid, and protocatechuic acid such a type of phenolic compounds can be found in bael fruit juice [3]. From A. marmelos fruit phytochemicals such as terpenoids, flavonoids, saponins, tannins, and glycosides can be easily isolated [6]. It has been reported that compounds include γ-sitosterol, rutin, β-sitosterol, glycosides, marmeline, aegelin, marmesinin, halfordiol, phenyl ethyl, lupeol; such a type of phytochemicals can be present in a very good quantity in bael leaves [49]. Catechin, flavanols, flavones, lignin, tannins, and isoflavones fall under the polyphenol group. Lignan glucoside compounds have been isolated from the bark of A. marmelos tree [50]. 7, 8- dimethoxy-1- hydrox-yl 2-methyl anthraquinone and 6-hydroxy-1-methoxy-3-methyl anthraquinone have been reported to be isolated from A. marmelos [51], and skimmiarepin A as well as skimmiarepin C has been isolated from stem bark [52] (Table 3).

Phytochemicals	Bael parts	Analysis method	Biological activities
Coumarins	Leaves, seed, fruit, bark, root	Colorimetric method, permanganate oxidation method	Antioxidant, antidiabetic, Anti-inflammatory, analgesic agents
Alkaloids	Leaves, fruits	Hager’s test, Wagner’s test, Mayer’s test, Dragendorff’s test	anti-inflammatory, alpha-glucosidase inhibitor, antibacterial, analgesic effects
Phenolic acids	Fruit	LC-MS, HPLC studies, Ferric chloride test	Antioxidant Activity
Terpenoid	Leaf, fruit, and bark	Noller’s test	Anticancer And antimalarial
Flavonoids	Fruit	Shinoda’s test	Antioxidant activity
Tannins	Unripe bael fruit	Gelatin test, Goldbeater’s test	Antimicrobial, helps in reducing blood pressure
Fatty acid	Seed, fruit, leaf	Gas chromatography with a flame ionization detector	Antimicrobial activity

Table 3.

Major phytoconstituents, analysis method, and biological activities of bael plant.

7. Quantitative analysis of phytochemicals

From the nutritional composition of A. marmelos, it is well known that the fruit is highly rich in various bioactive phytochemicals. It has been observed from various research studies that different types of phytochemicals or bioactive compounds are present in A. marmelos. Main class of phytochemicals are generally estimated as total phenolic count (TPC), total flavonoid content (TFC), and total carotenoids (TC). TPCs are responsible for anticancer activity of A. marmelos. For estimation, different processes are used, and for a particular process, there is taken a compound as a standard. For example, Folin–ciocalteu (FC) assay is used for TPC estimation with gallic acid as a standard. Similarly, TC is estimated by Gross method, and TFC estimation involves AlCl₃ colorimetric assay where rutin or catechin standard is used. Pearson’s method is generally used for the determination of ascorbic acid, and for total alkaloids ammonium hydroxide precipitation method is used. In pulp, TPC 87.3 4 mg GAE/g dw, TFC 15.20 mg CE/g dw (catechin equivalent per gram), vitamin C 26.1 7 mg /100dw and TC 32.98 μg/g dw is present [53]. In leaf, it has been observed that there are present TFC 63.9 mg/g, total phenolic content 29.4 mg/g, alkaloids 16.0 8 mg/g, and tannins 10.5 4 mg/g [54]. In flower, TFC ethanol extract is found to be 1615.2 mg GAE/g (gallic acid equivalent/g), and aqueous extract is found to be 1496.7 mg GAE/g [55]. In bark, it has been found that total phenolic content is 14.2 mg GAE/g [56].

8. Medicinal effects of bael

8.1 Antidiarrheal activity

Figure 3a and b shows the biological importance of A. marmelos for the treatment of various diseases. The powder form of A. marmelos fruit is similarly effective as its fresh form. Ripe or unripe fruit is useful for the treatment diseases such as diarrhea and dysentery due to its antiprotozoal activity and also useful for treatment of constipation. In chronic dysentery, it helps to reduce bleeding, and stool loosens [57, 58, 59]. The crude aqueous extract of A. marmelos fruit has been reported to be nonmutagenic to Salmonella typhimurium strain TA 100 in the Ames assay [18]. Over 35 strains of bacteria that cause diarrhea, Vibrio cholera, Escherichia coli, and Shigella sp are effectively inhibited by ethanolic extract of fruit [5, 60]. Recent research studies focused on the improvement of efficiency of medicines made of A. marmelos for diarrhea and dysentery, and it has been observed that the chloroform extract of bael root can perform same functionality as Ciprofloxacin with the advantage of no side effects [61].

Figure 3.

Biological importance of Aegle marmelos for the treatment of various diseases and mode of action.

In vitro and in vivo studies of A. marmelos make it more effective and provide economic feasibility for medication. The unripe fruit pulp of A. marmelos shows effective potential activity over enterotoxins and also responsible for preventing the formation of gut epithelium colony [61]. Antidiarrheal activity of A. marmelos is not only shown by unripe fruit pulp but also by leaf, juice, and water extract of unripe fruit, and it can be observed as minimum inhibitory concentration (MIC) method [62, 63, 64, 65]. Astringent properties of tannin present in A. marmelos functionalize nicely over diarrhea [66, 67]. It has been observed in Ames assay that A. marmelos can show nonmutagonic behavior to S. typhimurium strain TA100 [68, 69]. Hydroalcoholic extract of fruit is found to be nontoxic within the dose of 6 g/kg in mice [70]. It has been reported in pharmacological studies over animals that no adverse effect found after giving same dose of A. marmelos fruit extract for 30 days in which the maximum dose is 250 mg/kg of the body weight [53, 70, 71]. A. marmelos has its antigardial effect from decoction of unripe fruit [69]. Colonization studies of E.coli B170, E. coli E 134, and Shigella flexneri reported that colonization can be decreased by inhibiting bacterial entry [69]. The experiment of unripe fruit extracts over albino rats with inflammatory bowel disease (IBD) shows that it is very effective to reduce the intestinal inflammation. The reduction of intestinal inflammation of albino rat by the action of inflammatory mediators present in unripe A. marmelos fruit extract, and these are Interleukin 1, Interleukin 6, Interleukin 8, and tumor necrosis factor (TNF-α) [72]. The unripe fruit extract can also prevent intestinal mortality and secretion, which is an effective indicator of antidiarrheal action [73].

8.2 Antimicrobial activity

It has been reported that A. marmelos can protect against a wide variety of pathogenic organisms such as antibacterial, antitumor, antiviral, anti-inflammatory, antifungal [1]. Marmelide, which is extracted from A. marmelos, has been found to have more potential and economical than ribavirin, which is an antimicrobial drug activity (Figure 3b). The primary phase of a replicative cycle such as adsorption as well as penetration can be inhibited by marmelide, which shows due to the virucidal activity [74]. Dhar et al. show the A. marmelos juice acquired antiviral potential against the Ranikhet disease virus [75]. A study of A. marmelos fruit extract by Rani and Khullar in 2004 has been reported that Salmonella typhi is well affected by methanolic extract. The antimicrobial action of essential oil extracted from A. marmelos not only affects S. typhi but also effectively reduces the spore germination assay of pathogens [76]. Different concentration of A. marmelos extract has different inhibition rate such as 0.05% extract dose can prevent 100% over fungi, whereas 0.04% dose can have 90% prevention and 0.03% dose having 75% prevention [77]. Antimicrobial action can also be observed in A. marmelos juice, fruit, and leaf extract. A. marmelos leaf extract is very much effective over Filariae [78] and also intestinal parasites such as Ascaris lumbricoides and Entamoeba histolytica can be prevented by fruits and its powder, which is a great advantage over other plants, and it is economically feasible [79]. A. marmelos seeds also take part in this action, and it has been observed in the disc diffusion assay that an anthraquinone observed in Bael seed is effective over Candida albicans and Aspergillus species. Aflatoxin is a family of toxins produced by the fungus Aspergillus flavus, and it has adverse effects on the plants, but it can be easily prevented by the oil of A. marmelos leaf extract [80]. (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 and have possessed antimicrobial activity [81]. Klebsiella pneumonia, Entercococcus faecalis, Streptococcus faecalis, and Micrococcus luteus have been inhibited by A. marmelos fruit juice. Many times fish is attacked by the various pathogenic organisms, and this can be easily prevented by application of A. marmelos leaf extract. It is reported that for the survival of fish, the effectiveness of A. marmelos leaf extract enhanced with the dose of 5 g per Kilogram of the body weight. Leaf extract can enhance the hemoglobin level, pathogen clearance action except that it can also increase WBC count, lysosomal activity, and RBC count [81]. Dermatophytic fungi prevention is observed by methanolic A. marmelos extract with a concentration of 400 μg/mL [19]. A. marmelos extract prepared by using different solvents provides various applications with various concentrations of dose. Antiparasitic action of A. marmelos extract reported on cattle tick and 100% effective to prevent adult cattle tick and larvae of Rhipicephalus microplus with 0.3% methanolic extract. Besides this, 0.2% methanolic extract of A. marmelos can have 100% prevention over the larvae of R. microplus [82]. The concentration of 0.5–2 mg/mL of the extract of A. marmelos leaf is generally found very effective as an antifungal [83]. It has been reported that A. marmelos extracted by different methods and by using different substances such as petroleum ether, chloroform, methanol, etc., have different activities over different species [84]. A. marmelos extract can reduce the production rate of CD4þ T-cells CEM-green fluorescent protein in the human body affected by human immuno deficiency virus (HIV-INL4.3) [85]. Enterococcus faecalis can be prevented by the application of acetone extract of green fruit, which produces xanthoarnol [83]. The dose of 40 mg/mL concentration of methanolic A. marmelos leaf extract is applied in Agar diffusion method for both the Gram-negative and Gram-positive bacteria [86]. The adverse effect of many organisms can be prevented by a quinone compound [87], and activities of Gram-positive bacteria by alkaloid Shahidine extracted from A. marmelos [88]. Both the Shigella flexneri and Shigella dysenteriae can shows its resistance properties over β-lactam, and these are more convenient to β-lactam antibiotics [89]. Bark of A. marmelos tree shows antibacterial activity over few specific bacterial strains by Agar diffusion method where the solvents used are methanol and hexane [90]. It contains α-phellandrene and α-pinene, which acquired antimicrobial activity, and this has been observed in the estimation of MIC by Agar diffusion method [91].

8.3 Antiulcer activity

A very common disease of the gastrointestinal tract is ulcer, which can be caused by oxidative stress and presence of Helicobacter pylori bacteria. When mucosal flow of blood is restricted or gastro protection diminished, then the H. pylori bacteria affect widely as a result ulcer occurs [92]. It has been observed that A. marmelos seeds provide protection against aspirin-induced ulcer or pylorous-ligated ulcers on rats [93]. An A. marmelos seed contains a pyranocoumarin class compound named Luvangetin, which is responsible for antiulcer activity and very much depends on antioxidant mechanism [94]. Oral use of methanolic extract has great advantage over other medicines such as injections, and it is easier to be administered orally. In another experiment on rats that have lipopolysaccharide-induced ulcer after taking methanolic A. marmelos extract, improvement against ulcer is remarkable [95, 96]. It is reported that methanolic and aqueous A. marmelos extracts have effective antiulcer activity because they contain quercetin as antioxidant phytochemical [97].

8.4 Anticancer activity

Cancer is very big and challenging issue to survive as a healthy life in current world. The main reasons for cancer are hectic lifestyle with slow rate poisonous food. This leads to oxidative stress, which makes an easy pathway for cancer, very common disease [98]. Leaf extract of A. marmelos was found to be effective in inhibiting the growth of cancerous cell such as erythroleukemic HEL, T-lymphoid jurkat, melanoma Colo38, leukemic K562, breast cancer cell lines (MDA-MB 231) (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma), and Michigan Cancer Foundation-7 (MCF7), and B-lymphoid can be restricted by leaf extract of A. marmelos [61, 99]. Studies conducted showed that the phytoconstituents cineole, eugenol, citral, d-limonene, lupeol show antineoplastic effects. One of the important phytochemicals marmelin (1-hydroxy-5, 7-dimethoxy-2-naphtha- m-carboxaldehyde) has been found in bael, which exhibits anticancer activity against human colon cancer (HCT-116), human epithelial type 2 (HEp-2), and alveolar epithelial carcinoma cells [100]. Marmelin can also be effective to inhibit the growth of cancerous cells, leads to apoptosis, biochemical events through the induction of activation of TRADD (TNFR1-associated death domain protein), TNFα (tumor necrosis factor alpha), caspase-8, TNFRI (tumor necrosis factor receptor 1), and t-Bid, activates caspase-3 by releasing cytochrome C [101, 102]. Lupeol shows an antineoplastic effect on different neoplastic cell lines such as hepatocellular carcinoma cells, human epidermoid carcinoma cells, prostate carcinoma cell lines, human melanoma cells, and human pancreatic adenocarcinoma cells [103]. Citral is also effective to reduce the cell growth of cancerous cells by inducing apoptosis. On the other hand, Eugenol showed significant cytotoxic effects and is capable to act against malignant Caco-2 colon cells, normal human gingival fibroblast (HGF), human melanoma cell line, salivary gland tumor cell lines (HSG), and malignant HepG2 hepatoma cells [101, 102]. A. marmelos can show its chemopreventive action due to the presence of some important phytochemicals such as eugenol, citral, limonene, etc. [104, 105].

8.5 Anti-inflammatory activity

Inflammation is a defense mechanism and is activated when invader pathogen or foreign particles attack our system. Many indicators are there, which reflect inflammation very well; these are swelling, heat, pain, redness, etc. [67]. A. marmelos fruit extract shows anti-inflammatory function because of the presence of phytochemicals such as lupeol, skimmianine, and citral [106]. The main function of these phytochemicals, which are present in A. marmelos, is inhibiting the histamine-mediated signaling [106]. The ripened fruit juice can prevent inflammation of rectum. It has been reported that histamine-induced contraction can be antagonized by A. marmelos leaf and induce positive relaxant effect in the affected area [19].

8.6 Antipyretic activity

Antipyretic function in human is to lower down the body temperature. This is required only when there is fever or illness. Allopathic medicines can do that, but it has side effects, whereas A. marmelos plant part extracts can do the same thing without any side effects [107]. This advantage of A. marmelos provides a good health and lowers the expense of medicines. It has been observed in the experiment with albino rats that the temperature is decreased after applying ethanolic extract of A. marmelos with a dose of 200 and 400 mg per kilogram of the body weight. The body temperature reducing action of the ethanolic A. marmelos extract is comparable with paracetamol at a dose of 100 mg per kg of the body weight [19, 108]. Phytochemical compounds such as acetone, petroleum ether, ethanol, chloroform, diethyl ether are responsible for the antipyretic actions, and paracetamol equivalence is majorly due to the chloroform and methanol extract of A. marmelos [109].

8.7 Antispermatogenic activity

A. marmelos can affect the capability of fertility in male candidates. Generally fruit, leaf, and seeds can play this antifertility activity. Marmin and fagarine can reduce the fertility activity of male, and these two compounds are found in bark extract of A. marmelos in greater amount. It has been reported that methanolic extract of A. marmelos can reduce the serum testosterone level and also reduce the weight of the reproductive organ [61]. This reduction depends on the concentration of the dose taken and time duration [61]. Sperm viability, density, motility, and sperm acrosomal integrity all these can reduce by the effect of methanolic extract of A. marmelos. Condensation and degeneration of nuclear chromatin and exfoliation of extended spermatids were found in the study of histopathology and the availability of space within germinal epithelium denoting necrosis and testicular cytotoxicity. The experiment on rats has been observed that A. marmelos extract affects infertility, but this is temporary and totally time- and dose-dependent, and the most important thing is after the removal of the treatment, there is a complete restoration of morphological and physiological parameters [110]. It opens a new possibility to the development of herbal contraceptive for males because it can stop fertile power, and after the removal of treatment, it can do complete restoration of the fertile power [111].

8.8 Diuretic activity

Through urination, our body expels out the salt and other materials with water and balances body temperature and water level. Those suffering from water retention and anxiety need medication. A. marmelos leaves and roots are natural source of providing diuretic activity to increase urination level for such individuals, whereas roots are more beneficial than leaves. At higher dose (500 mg/kg) ethanolic extracts of A. marmelos fruit result in significant increase in sodium excretion. Extracted fraction of ethyl acetate, petroleum ether, and chloroform of A. marmelos fruit showed effective diuretic activity [61].

8.9 Antigenotoxic activity

Antigenotoxic activity of A. marmelos fruit extract can be estimated by using the peripheral human blood lymphocytes and E. coli PQ37. Chromotest (E. coli PQ37) SOS response is induced by aflatoxin B1 and H₂O₂, and it is prevented by the acetone and methanol. In general, SOS response is a response to DNA damage, in which cell cycle is arrested followed by DNA repair and mutagenesis is induced. Genotoxicity of aflatoxin B1 and hydrogen peroxide is inhibited by 84.65 and 70.48%, respectively, by the action of methanol extract of A. marmelos fruit [19]. Presence of different polyphenolic components in the fruit extract accounts for the antigenotoxic activity and has the ability to save DNA from the S9-dependent mutagens and reactive oxygen species. Several researchers revealed that in metabolism of aflatoxin B1, the enzyme activity can be inhibited by the polyphenols present in A. marmelos fruit extract [112].

8.10 Radioprotective activity

Radiotherapy is used in the treatment of cancer, but it has some side effects, which are harmful. The side effect occurs due to invariable exposure of radio sensitivity to the cytotoxic effects of ionized radiation on treatment. At the time of ionized radiation treatment, many cells are damaged because of the formation of free radicals, which can be effectively countered by antioxidant compounds [113]. It has been reported that bael fruit juice has potential to minimize the effect of free radicals; as a result, the severity reduces and survival probability is enhanced in mice [114]. In the radiation treatment of mouse in intestine and bone marrow, the detrimental effect of radiation is significantly reduced by A. marmelos fruit extract [115]. The hydroalcoholic extract of A. marmelos when administered intraperitoneally in mice has been watched that there is increase in survival rate after exposure to gamma radiation at a lethal dose of 10 Gy [116]. The inhibition power to the radiation of A. marmelos fruit and leaf extracts is due to free radical scavenging and lipid peroxidation associated by the improvement in GSH concentration in the spleen, kidney, intestine, and liver [115, 117]. On comparison of inhibition power to the radiation between the A. marmelos plant parts, then the leaf extract was found better, and this can provide extra protection from hematopoietic and gastrointestinal damages.

8.11 Antidiabetic activity

Nowadays, one of the very common diseases is diabetes mellitus. Stressful lifestyle, fastfood consumption, and genetic issues make diabetes a very common disease [118]. Specially, oxidative stress of the body is closely related with this disease. A. marmelos fruit juice increases the utilization of glucose by stimulation and the effect looks like similar to the function of insulin [119, 120]. Fruit juice can improve blood circulation by dilating the blood vessels; as a result of this, blood clot formation is reduced, which helps to remove diabetes (Figure 3a). Amino acids and dietary fiber are present in the fruit juice of A. marmelos and can absorb moderate sugar and promote insulin sensitivity [40]. A. marmelos fruit extract shows multifunctional activity over diabetes, it is not only reduces the glucose level in blood and glycosylated hemoglobin but also simultaneously enhances the plasma insulin as well as glycogen in diabetic rats [121]. It has been reported that methanolic extracts of A. marmelos leaf reduce the level of glucose in blood of Wistar albino rats according to the doses applied; as it increases, the serum insulin and so the level of glucose automatically decrease [122, 123]. Insulin secretion can be affected by coumarin, which is present in A. marmelos fruit juice [124]. Both the ways of administration means oral and intraperitoneal exhibit hypoglycemic effect. The main mechanism of action of A. marmelos is improvement of insulin secretion or stimulation of glucose or both.

8.12 Wound-healing activity

Wound healing is a multistep process and involves different techniques such as contraction of collagen lattice production, cell proliferation, inflammation, etc. Pain is the common symptoms of wound, and main key factor for wound healing is the discharge of reactive oxygen species (ROS), which helps in healing [125]. In an experiment, reports on the Wistar albino rats showed that methanolic A. marmelos seed extract ointment can recover the wound perfectly [126]. The functionality of A. marmelos on wound healing is like that of nitrofurazone drug [127]. Healing process is boosted when myeloperoxidase (MPO) level and free radicals touch the minimum level. On the other hand, if antioxidant activity increases, then the rate of healing mechanism is also increased. The phytochemicals present in A. marmelos are very much effective for wound healing because they can increase the antioxidant activity [24].

8.13 Immunomodulatory effect

A. marmelos can improve the immunity upto a particular stage depending on the situation. It has been observed that after oral administration of different doses of A. marmelos, both the neutrophil adhesion and phytogenic index are increased. Bovine pasteurella multocida can reduce the mortality rate in mice at both low and high doses. Administrations of lower doses are much more effective than higher doses [128]. Another study on fish reported that survival chances are more with A. marmelos leaf administration [129]. Bael can increase enzyme activity, RBC count, and WBC count, which can lead to a healthy system; as a result, immunity is increased.

8.14 Nephroprotective activity

A. marmelos leaf extract shows its nephroprotective function. Nephrotoxicity is mainly observed due to the enhancement of blood urea nitrogen, serum creatinine, and MDA level. The study of gentamicin nephrotoxicity reported that A. marmelos leaf extract can dominantly reduce the enhanced level of MDA, blood urea nitrogen, and serum creatinine [130]. The cisplatin-promoted nephrotoxicity can also be protected by A. marmelos leaf extract [131].

8.15 Antiasthmatic activity

In phelgm and asthma, decoction of A. marmelos leaf can reduce these effectively. Guinea pig ileum study reveals that antagonistic effect can be shown by tracheal chain on contraction produced by histamine [132, 133]. Histamine release from mast cells can be prevented by aegeline situated in A. marmelos leaf [134]. Histamine release is the main reason for asthma and phelgm. A. marmelos leaves effectively reduce the release of histamine; that is why it is very helpful for controlling asthma.

8.16 Antithyroid activity

A. marmelos leaf extract can reduce the enhanced level of thyroid hormones in serum. This function of A. marmelos leaf is due to the presence of scopoletin in it, which is actually responsible for the reduction of thyroid hormones in serum. The activity of Scopoletin is as close to the activity of Propylthiouracil [135]. The dose is experimented on thyroxine-treated animals and found that Scopoletin 1 mg /Kg for seven days is most effective.

9. Conclusion and future prospectives

In recent years, scientific studies have validated many of the ethnomedicinal uses and reports on various parts of A. marmelos. A. marmelos has immense medicinal actions over animals, and it may replace many medicines of allopathy. The functionalities of many allopathic medicines can be done by different parts and its extracts of A. marmelos. As a result, this not only reduces the expense of medicines but also reduces the chances of new other diseases as it has no side effects. This is a great advantage over allopathy medicines, and simultaneously it is economically feasible. The phytochemicals present in A. marmelos are very effective, and these are responsible for the various therapeutic activities, and this is the reason for more investigation and research required to know the functionalities of phytoconstituents at molecular level, which can provide more efficient medicine. Planting this tree is very easy and simple; therefore, the availability is fruitful, which is a great advantage. Each and every part of this tree can be used as a medicine, so all the parts are in use, which reflects more marketing from one tree; it enhances the productivity, and economically there is a profitable position for the manufacturer industry. This review article tried to focus on the medicinal uses with economically feasible production and marketing and found exceptionally well, although more research required for the improvement of medicinal functionalities and productivity.

Acknowledgments

This scientific work has been funded by the TATA College, Kolhan University, Chaibasa, India.

Conflicts of interest

The authors declare that there is no conflict of interests regarding the publication of this article.