An Overview on Phytochemistry, Pharmacology, Pharmaceutical, Traditional and Economical Aspects of Aegle marmelos

 

Nikita Kumawat1, Jidnyasa Pantwalawalkar2, Yogini Vispute1, Rahul Tade3, Sopan Nangare3*

1Department of Pharmaceutics, H. R. Patel Institute of Pharmaceutical Education and Research,

Shirpur; 425405, Dist- Dhule (MS), India.

2Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy,

Kolhapur; 416013, Dist- Kolhapur (MS), India.

3Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur; 425405, Dist- Dhule (MS), India.

*Corresponding Author E-mail: snangareopan@gmail.com

 

ABSTRACT:

Aegle marmelos (A. marmelos Corr., Rutaceace) known as bael is found from pre-historic time. It belongs of Indian origin. It has abundant allegorical importance for Hindus. A. marmelos is available in diverse varieties viz. Pant Aparna, Pant Urvashi, Narendra bael-5, Narendra bael-6, Pant Sujata, Pant Shivani, CISHB-1, CISHB-2, etc. Wholly parts of the A. marmelos tree have medicinal values and have been used as medicine for a long time. A. marmelos has different classes of compounds including coumarins, alkaloids, terpenoids, fatty acids, amino acids, etc. This plant has a strong potential to treat diseases including diarrhea, dysentery, anti-bacterial, anti-fungal, diabetes, peptic ulcer, inflammation, etc. Besides, it provided anticancer, cardio-protective, antipyretic, analgesic, constipation, antioxidant, wound healing activity. The gum obtained from bael fruits has great potential in sustaining the delivery of the drug. The marketed products of A. marmelos are Chyawanprash, A. marmelos capsules, Capsule Bilv Giri, Entrostat Syrup, Ojamin, Vilwadigulika, etc. Other products made from fruit are jam, slab, dehydrated bael, fruit squash, fruit pulp Bael powder, toffee, and ready to serve (RTS) drink. Recently lots of work on different parts of bael has been establishing scientific proof for its traditional claims. Hence, it is essential to compile the current findings along with the preceding work, which will assist the researchers to find all the literature on A. marmelos. Overall, the present overview deals with general, traditional, phytopharmaceutical, pharmacological, chemical profile, and economic importance like pharmaceutical and other applications.

 

KEYWORDS: Aegle marmelos, Bael, Pharmaceutical Applications, Pharmacological Profile, Phytopharmaceutical Profile.

 

 


INTRODUCTION:

Aegle marmelos (A. marmelos Corr., Rutaceace)1 belongs to the family of citrus fruits. It is a plant of Indian origin having huge therapeutic potential2. Unfortunately, it is not fully employed3. A. marmelos is used for the worship of Lord Shiva from ancient times. Thus, it is widely known as the tree of Shiva. Almost every part of A. marmelos such as flowers, fruits, stems, leaves, roots, barks, etc. has been utilized in a variety of Ayurvedic medicines from ancient times to manage certain severe disorders/diseases including cancer, constipation, ulcer, diarrhea, dysentery, and many others4. A. marmelos is also known as the environmental protector as bark and leaves act as a sink by absorbing dust and poisonous gases from the surrounding atmosphere and makes them clean. Therefore, bael falls in the category of “climate purifiers”. It emits a greater percentage of oxygen in sunlight as related to other plants5. A. marmelos is known as Mahaphala because of its limitless uses6. In a nutshell, the present summary of A. marmelos deals with a general introduction, chemical profiles, pharmacological use, pharmaceutical applications, and their economic importance.

 

Plant profile:

Detail scientific classification7,8 and vernacular names8 of A. marmelos are depicted in table-1 and table-2 respectively.

 

Table 1: Scientific classification of A. marmelos

Kingdom

Plantae

Order

Sapindales

Family

Rutaceace

Subfamily

Aurantioideae

Genus

Aegle

Species

Aegle marmelos

 

Table 2: Vernacular names of A. marmelos

Language

Vernacular names of A. marmelos

English

Bael fruit, Bengal quince, Indian quince, Golden apple, Stone apple

Hindi

Sirphal, Bel, Bili, and Bela

Sanskrit-

Asholam, Atimangaliya, Bilva, Adhararutha

Gujarat

Billi

Telugu

Maredu, Sailushamu, Bilvumu, Maluramu, Sandiliyamu, Sriphalamu

Tamil

Iyalbudi, Aluvigam, Kuvilam, Vilwam, Villuvam, Mavilangai

Malayalam

Koovalam, Vilwam

Bengal

Bel, Bael

Kannada

Bilva, Bela

Orissa

Belo

 

 

Varieties of A. marmelos fruit:

Plentiful literature reported that A. marmelos fruit varies are available, which contains different specifications. In this section, we have discussed the varieties of A. marmelos fruit. Different varieties of bael are depicted in Table-34,9,10.

 

Botanical description:

Bael is a slow-growing and medium-sized tree, with a short trunk, soft, peel off the bark, thick, and spreading. The borne singly or in the group, alternate leaves, are contented of 3-5 ovals, pointed, and superficially toothed leaflets. The fruit is pear-shaped, oval, round, and its diameter range up from 5 to 20cm11.

 

Soil type:

A. marmelos grows in rich, well-drained soil, soft, alkaline, or stony soils (pH 5- 8)12.

 

Tree management:

The tree has no exacting cultural necessities, during well with a least of irrigation and fertilizer. In 6 to 7 years seedlings begin to bear. Up to 15 years complete production is reached. When fruits are yellowish-green, they are harvested and reserved for 8 days up to lose their green tint. After that, the fruit separates from the stem. The tree can produce many more as 800 fruits per season12.

 

Origin and distribution:

The A. marmelos has its beginning from Central India and the Eastern Ghats. In India, it is found growing wild in specially sub-Himalayan tracts. Bael is originally growing in Himalayas, Bihar, Uttaranchal, Madhya Pradesh, Jharkhand, and Chhattisgarh. In addition, bael is also grown in various Egyptian gardens in Surinam and Trinidad13.

 

Bael in mythology:

The bael is one of the divine trees of the Hindus. Leaves are offered prayers to Shiva and Parvati since ancient times. Bael is a shed sacred tree, associated with7. God's having useful medicinal properties, especially as a new cooling agent14.

 

 

Nutritional values:

Nutritional values of A. marmelos fruit (% or per 100g)8,15,16 are tabulated in Table 4.

 

Chemical composition

Diverse chemical constituents like coumarins, steroids alkaloids have been secluded and known from diverse tree parts such as wood, root, fruits, leaves, and bark7,8. In this section, we have enlisted the chemical composition of A. marmelos (Table 5).


 

Table 3: Different varieties of A. marmelos

Name of Variety (Recommended area)

Developed at

Fruit size

Shape

Surface

Mucilage content

Seed

Pulp color

Narendra Bael-4 (Uttar Pradesh)

Minimum fruit weight, fruit length and fruit breadth.

---

---

---

---

---

---

Narendra Bael-5 (Uttar Pradesh, Rajasthan, Bihar Jharkhand)

---

Medium-sized (about 1 kg weight)

Round

Smooth

Low

Medium

Pale yellow

Narendra Bael-6 (Uttar Pradesh)

Narendra Dev Krishi College, Faizabad.

Medium-sized (about 600 g)

Round

smooth

Low

Maximum

---

Narendra Bael-7 (Uttar Pradesh)

---

More than 2.00 kg

Elliptical

Smooth

---

Maximum

Pale yellow

Narendra Bael-9 (Uttar Pradesh)

---

---

Ovate

Rough

High

Minimum

Dark yellow

Narendra Bael-16 (Uttar Pradesh)

---

Av. weight 1.3 kg

Elliptical, round

Rough

High

Maximum

Pale yellow

Narendra Bael-17 (Uttar Pradesh)

---

Oblong, big-sized

---

---

Low

Minimum

Yellow

Pant Bael-10 (Uttar Pradesh)

---

---

---

---

---

---

---

Pant Shivani (Uttarakhand)

Pant Nagar Krishi University.

 

More than 2.00 kg

Ovoid, oblong

Smooth

Medium

Maximum

Yellow

Pant Aparna (Uttarakhand)

Pant Nagar Krishi University.

Small size (0.6-0.8 kg),

Globose

Smooth

Low

Low

Yellow

Pant Sujata (Uttarakhand)

Pant Nagar Krishi University

Low (<0.1 kg)

Round

Rough

High

---

Yellow

Pant Urvashi (Uttarakhand)

Pant Nagar Krishi University

1.6 kg

Ovoid

Smooth

---

---

Dark yellow

CISHB-1(Lucknow)

Central Institute for Sub-tropical Horticulture, Lucknow.

Low

(<0.1 kg)

Ovate

Smooth

---

---

Dark yellow

CISHB-2 (Lucknow)

Central Institute for Sub-tropical Horticulture, Lucknow.

more than 2 kg

Elliptical

Smooth

High

---

Pale yellow

 

Table 4: Nutritive value of bael fruit (% or per 100g)

Components

Value (%)

Components

Value (%)

Water (moisture)

64.2

Potassium

0.6

Protein

1.8

Iron

0.3

Fat

0.2

Vitamin A (IU)

186

Mineral

1.5

Vitamin B1

0.01

Fiber

2.2

Nicotinic acid

0.9

Carbohydrate

30.6

Riboflavin

1.2

Calcium

0.09

Vitamin C

0.01

Phosphorus

0.05

Calorific value

129

 

Table 5: Chemical composition of A. marmelos

Chemical class

Phytoconstituents

Coumarins

Marmelosin is the principal constituents existing in bael fruit gum. The coumarins class containing other components including marmin, alloimperatorin, xanthotoxol, scoparone, gummarmesin, imperatorin, methyl ether, scopoletin, umbelliferone, psoralen, and marmelide are present in A. marmelos. Marmenol, 7-geranyloxycoumarin has also been stated.

Alkaloids

 

Marmeline, dictamine, aegelin, aegelenine, fragrine are some alkaloids present in the bael tree.

Polysaccharides

Galactose, arabinose, uronic acid, and L-rhamnose are obtained on hydrolysis.

Seed oil

Palmitic, stearic, oleic, linoleic and linolenic acid.

Tannins

 

In January, more content of tannin in bael fruit was noted. There is as much as 9 percent tannin in the pulp of wild fruits and less in cultivated form. Also, tannin is present in leaves in form of Skimmianine.

Carotenoids

 

The pale color of the fruit is due to the presence of Carotenoids. Marmelosin, Skimmianine, and umbelliferone are the therapeutically main component of the bael plant.

 

Traditional uses:

Nearly whole parts of the bael tree are medicinally useful8 like flower, fruit pulp, leaves, root, stem bark, etc17. In this section, we have discussed the traditional uses of A. marmelos.

 

Leaves:

Leaves act as a mild laxative and are used for asthma. The leaf juice of bael is given in dropsy/abnormal accumulation of liquid in the cellular tissue followed by jaundice and constipation. The decoction of bael leaves is given to reduce elevated body temperature (fever) and is also preferred as an expectorant. In the case of irritation of the conjunctiva or other parts and bronchitis hot poultices are applied.

 

Root:

The alcohol is present in the root and sometimes the stem and bark are valuable in intermittent fever, also in hypochondrias, and palpitation of the heart. It is the root of the ingredients of Ayurvedic formulation Dasamoola, the standard for loss of appetite and puerperal diseases e.g. Inflammation of the uterus.

 

Flower:

The drug obtained after the distillation of flowers is used as a tonic for the intestine and stomach. Besides, it is used as an anti-dysenteric, antidiabetic, local anesthetic, and expectorant. It can be used in the case of epilepsy.

 

Fruit:

A. marmelos fruit is eaten during convalescence after diarrhea. It works as mild astringent and as anti dysenteric. The dry powder of fruit including mustard oil is used for treating burn cases. Fruits are also used in epilepsy, constipation, gastric troubles, and ulcer. The fruit is employed as a digestive brain and heart tonic, laxative, antiviral.

 

Ripe fruit:

The ripe fruit stimulates digestion and treats inflammation of the rectum. The ripe fruit extract showed antiviral activity against the Ranikhet disease virus. The pulp of ripe fruit is sweet, cooling, aromatic, and nutritive when taken fresh. Fresh juice has an unpleasant taste while pungent fruit extract is used to lowers blood sugar.

 

Unripe fruit:

The unripe fruit is used as a tonic, demulcent, digestive, and astringent. A concentrate of unripe fruit is astringent and used as an astringent in diarrhea and severe dysentery.

 

A. MARMELOS AS A PHARMACEUTICAL:

The immature fruits of A. marmelos, popularly contain bioactive compounds such as alkaloids, phenolics, carotenoids, coumarins, terpenoids, flavonoids, etc.18. Interestingly, the bael fruit gum (BFG) is described to contain a high content of d-galactose and glucuronic acid ie.,54.26% w/w and 20.8% w/w respectively [19]. Because of the existence of more d-galactose concentration BFG can be estimated to have well water solubility and water-retaining capacities. Together with more d-galactose and galacturonic acid content can be predicted to be very effective in granting high solubility of BFG, making it useful for several applications in the modification of drug release features and functional properties of food products19. Gums denote a category of natural polymers capable of forming extremely viscous aqueous solutions or dispersions. The bael gum indicates the presence of free -COO- moieties and, acts as anion and bind with cationic moiety to produce polyelectrolyte complex. These are possible because it contains galactouronic acid. Polyelectrolyte complex is, used to control and sustain drug release20. In tablet manufacturing, BFG acts as a binder,21 while in liquid form it is used as a stabilizer or suspending agent22. BFG is biocompatible, low cost, relatively ample available23 as compared to their synthetic counterparts. Few pharmaceutical applications have been depicted in Table-6.

 

Table 6: Pharmaceutical applications of A. marmelos

Sr. No.

Drug

Formulations

Role of BFG

Effect

Ref

1.                     

Paracetamol

Tablet

Binder

Improved the hardness

24

2.                     

5-Fluorouracil

Microsphere

Carrier

Cross-linking

25

3.                     

Levamesole

Tablet

Mucoadhesive

Controlled release

26

 

General uses of A. marmelos:

A yellow color derived from unripe fruit rind is used in printing. Flowers are used for cooling beverages while stem gum is used for adhesion and bookbinding. Wood is used for house building, cart construction, combs, and different household articles. Leaves are used in chew sticks, toothbrushes, fodder. The entire tree is used as a barrier to wind27.

 

Processed product:

Several such products have been made from A. marmelos. Bael fruit is used to prepare candy, fruit pulp, fruit squash, dry bael, RTS drink, panjijri, toffee, jam, slab, bael powder, etc.27.

 

REPORTED PHARMACOLOGICAL ACTIVITIES:

Antimicrobial and antiviral activity:

Bael extract shows antiviral as well as, antimicrobial activities28,29. It is, active against, species like Escherichia coli (E. coli) Staphylococcus aureus (S. aureus), Salmonella typhimurium, Proteus vulgaris, Bacillus subtilis30. The essential oil obtained, from the A. marmelos leaves shown antifungal action against animal and human fungi such as Microsporum gypseum, Trichophyton rubrum, Microsporum audounii, Trichophyton mentagrophytes, Microsporum cookie, Aspergillus flavus, Epidermophyton floccosum, Aspergillus niger, and Histoplasma capsulatum. A. marmelos leaf extracts and fractions have revealed fungicidal activity against a range of clinical isolates of dermatophytic fungi. Various extracts of bael leaves, fruits, roots have been noted to be active against different bacterial strains. There are reports of antimicrobial activity of crude extracts made from plants. In 2009, Venkatesan et al. showed that ethanolic plus aqueous extract has an action against Pseudomonas aeruginosa, E. coli, S. aureus, and Bacillus subtilis. The aqueous extract show comparatively less activity than the ethanolic extract. Maximum antibacterial activity was shown against Bacillus subtilis followed by E. coli, S. aureus, and Pseudomonas aeruginosa. Jyothi and Rao indicated that hexane, cold methanol, and hot methanol extracts have inhibited Entercococcus faecalis, Streptococcus faecalis Klebsiella pneumoniae, Micrococcus luteus growth in vitro. And also three extracts do not affect E. coli as well as Proteus vulgaris31,32.

 

Antidiarrhoeal activity:

Dry fruit pulp and powder are used to treat diarrhea. The dried-up powder is often used for diarrhea and constipation alternative7. Antidiarrhoeal activity of chloroform extract of root was performed in vitro and in vivo by Mazumder et al. The extract shows the same activity as ciprofloxacin and generally active against the strains of Vibrio cholera, as well as E. coli and Shigella spp33,34. A. marmelos unripe fruit pulp affected the bacteria growth of the intestinal epithelium and the development and effect of some pathogens. It suggests the multiple different mechanisms of action of A. marmelos in communicable types of diarrhea thus validated its use in old Indian texts and continuing use by communities to cure diarrhoeal diseases34.

 

Radioprotective effects:

The efficient employment of radiation therapy to treat cancer and palliative care is impaired by side effects occurring from the radiosensitivity of surrounding normal cells, which are usually subjected to the cytotoxic effects of ionization throughout therapy. In such a case, the use of radioprotective molecules that can protect normal cells from radiation injury is of considerable use. Radiation ill-effects are mainly because of the production of free radicals, and the antioxidant molecules that combat them are anticipated to be of tremendous benefit in their prevention. Abdullakasim et al. have noticed that fruit juice of A. marmelos had great measures of total phenolic compounds and is a good antioxidant. Transitional metals (iron) produce ROS using redox cycling. A. Marmelos is a strong chelator, and this may have led to the radioprotective and antioxidant effects observed. Inhibition of lipid peroxidation is critical in process of disease and involve free radicals, and research has shown that fruit leaf and extracts prevent radiation-induced peroxidation of lipid in the mice intestines, liver, kidneys, and spleens31. A. marmelos triggered concentration-dependent inhibition of H2O2 and iron-induced lipid peroxidation in mice. Leaf extract improved the activity of antioxidant enzymes SOD, glutathione peroxidase, and catalase in normal mice and diabetic rats. Radiation induces an inflammatory reaction by mediators and stimulates important physiological and immunological pathways. Immunity loss can occur with the reduction of immunocompetent cells that can cause amoral microbial infections. Immune activation is a defensive method and immunostimulants improve the overall immunity of the host by providing an unspecific immune response to pathogenic organisms. A. marmelos leaf extract increased overall peritoneal macrophages as well as splenic lymphocyte counts in mice, indicating that it produces immunomodulatory impact35.

 

Anticancer activity:

Cancer is a significant public health issue, the second-highest cause of death for both genders in both developed and developing countries. About 12.7 million new cases of various cancers (56 percent occurred in regions of development in the world) and 7.6 million cancer deaths (about 63 percent in regions under development) occurred in 2008. By 2020, forecasts report a 3-fold rise in the incidence of cancer, with a significant raise in cancer cases and deaths in developed countries with insufficient resources to address the issue. Studies have shown that the extract of Indian Bael has a major anti-proliferative impact. In vitro, it prevents the spread of tumor cell lines of human-like leukemia K562 and Tlymphoid Jurhat36. While preclinical tests have shown that A. marmelos leaf extracts have been effective to inhibit the overall growth of various cancer cells37.

 

Chemopreventive action:

Multiple experimental, as well as epidemiological reports, have shown that chemoprevention can provide an effective means of preventing cancer. A. marmelos fruit extracts have been found to have a preventive role against skin carcinogenesis induced by DMBA in mice. In Wistar rats, the methanolic extract of A. marmelos at a dose of 25 and 50mg/kg body weight was found to be effective to inhibit the diethylnitrosamine initiated and 2-acetyl aminofluorene promoted hepatocarcinogenesis. Studies have also revealed that the chemicals present in A. marmelos, such as limonene, citral, eugenol, lupeol, anthocyanins, and rutin have been found to possess chemopreventive effects38.

 

Antipyretic potential:

Shukla et al. estimated the antipyretic properties of A. Marmelos in albino rats on pyrexia (caused by Brewer's yeast). They observed that at doses of 200mg/kg body weight and 400mg/kg body weight, the ethanolic extract induced a substantial (P<0.001) reduction in increased body temperature on a dose-dependent basis. This antipyretic effect of prepared extracts was similar to that of standard paracetamol (100mg/kg body weight)17,39. Therefore, in the future it can be used as a potential antipyretic agent for the management of elevated body temperature.

 

Ulcer healing potential:

Bael fruits were used to treat peptic ulcers i.e. it creates a mucilaginous layer on the stomch gastric mucosa and prevents interaction of an acid with a mucosal layer40. Using indomethacin-induced ulceration, stressed induced ulceration, pylorus ligation triggered ulcerations, the A. marmelos seeds extract (methanol and aqueous) anti-ulcer activity was considered by Sharma. In this work, the doses of 200mg/kg and 400mg/kg body weight, the methanolic extract of bael seed showed considerably (P<0.01) ulcer protective action in all animal models. The bael seed aqueous extract was also found considerably (P<0.05) ulcer healing property at the same doses (methanolic extract). A significant increase in pH, free acidity, and total acidity and reduction in the volume of gastric juice was found in pylorus ligated rats. The antiulcer properties of both extracts were due to the existence of quercetin-like (flavonoid) contents. Further research suggested that A. marmelos fruit pulp extract-treated albino rats display a substantial decrease in catalase activity, superoxide dismutase, mucosal thickness, and glutathione levels. A significant boost in alanine aminotransferase, lipid peroxidation activity, aspartate aminotransferase, ulcer index was also observed. It concludes that antiulcerogenic properties and gastroduodenal protective of A. marmelos may depend on an antioxidant mechanism38,41. Consequently, in the future, it can be used as a potential ulcer healing agent.

 

Antigenotoxic activity:

Using E. coli PQ37 (SOS chromotest) and the peripheral human blood lymphocytes (Comet assay) Kaur et al. tested the antigenotoxic activity of A. marmelos fruit extracts. Acetone and methanol extract decreases the SOS response triggered by hydrogen peroxide and aflatoxin B1 in the SOS chromotest. Genotoxicity of H2O2 and aflatoxin B1 was inhibited by methanol extract by 70.48% and 84.65% respectively. These extracts exhibited a major fall in the tail moment by hydrogen peroxide (9μmol/L) carried out by single-cell gel electrophoresis assay. The antigenotoxic activity showed by the extracts can be due to the different polyphenolic compounds present in these extracts. Such compounds can protect DNA from S9-dependent mutagens and ROS. Several studies have shown that polyphenol-rich extracts can reduce the enzyme activity involved in the metabolism of aflatoxin B142. So, in the future, it can be used as a potential antigenotoxic.

 

Diuretic activity:

The diuretic function of several organic extracts and their parts of A. marmelos was examined in experimental models. Extracts were given intraperitoneally at doses of 500, 400, 300, and mg/kg to experimental animals (rats). Hence, the diuretic effect by measuring urine volume and sodium content in urine was estimated. It was found that ethanolic extract produces a considerable increase in excretion of sodium at a higher dose (500mg/kg). Ethyl acetate, chloroform, petroleum ether portions are also efficient43.

 

Antifertility activity:

A. marmelos leaf, seed, and fruit are considered to have a reversible effect on male fertility. Fagarine and marmin are obtained from A. marmelos bark extract and reduce male fertility. Agrawal et al. have found that by reducing reproductive organ weight and serum testosterone levels A. marmelos methanol extract induces dose and duration-dependent infertility. They also record reductions in sperm viability, density, motility, and sperm acrosomal integrity. Elongated spermatids exfoliation, condensation of nuclear chromatin, and degeneration were observed in test histopathological studies and the formation of spaces inside the germ epithelium, suggesting testicular cytotoxicity and necrosis. And time-dependent complete infertility was observed in the study. The authors also stated that the complete restoration of both morphological and physiological parameters in extracted rats was observed after the withdrawal of medication. These results indicate that the extract of A. marmelos is a good candidate for male contraception by its capability to induce full pregnancy inhibition, rapid recovery of fertility after removal from treatment38,44.

 

Anti-inflammatory activity:

Various organic extracts of A. marmelos leaves have a very subacute and strong acute anti-inflammatory activity. A. marmelos has demonstrated substantial anti-inflammatory activity and maybe a potential anti-inflammatory agent in chronic and acute inflammatory animal models it may be by the presence of lupeol and skimmianine. Histamine receptor activation is crucial for asthmatic and allergic evidence. An alcoholic extract from A. marmelos leaves have antagonized histamine-induced contractions and exhibited a positive relaxant effect in an isolated tracheal chain and guinea pig ileum, indicating inhibition of the function of the H1 receptor that this extract can underline these effects45. The anti-inflammatory property was investigated using the serial extracts of the A. marmelos leaves. The antipyretic and analgesic properties were also assessed. Many extracts of A. marmelos caused a carrageenan-induced paw edema major inhibition and cotton pellet granuloma in rats46.

 

Hypoglycemic and antioxidant activity:

The A. marmelos exhibited remarkable antioxidant acitivty47,48. A. marmelos fruit (AEAM) aqueous extract demonstrates the hypoglycemic49 and antioxidant effect in albino rats50,51.

 

Cardioprotective effects:

By the administration of leaf extract to an experimental animal in isoprenaline induced myocardial infarction, the cardioprotective effect was estimated52.

 

Hepatoprotective activity:

The experiments were conducted with four classes of animals. The experimental animals were administered 30 percent ethyl alcohol for 40 days and the fine raw leaf powder was fed to the animals for the next 21 days. The experimental results show that A. marmelos leaves have an excellent hepatoprotective activity53.

 

Immunomodulatory activity:

A. marmelos fruit (MEAM) methanolic extract was used to carry Immunomodulatory action by neutrophil adhesion test plus carbon clearance assay. Whereas, humoral immunity was examined by mice lethality test plus indirect haemagglutination assay54.

 

Insecticidal activity:

The insecticidal operation was conducted to assess the potential for the use of essential oil from A. marmelos leaves to control insect infestation of wheat from Rhyzoperthadominica (F) and stored grams from Callosobruchuschinensis (L)55.

 

Testicular activity:

A. marmelos aqueous leaf extract at 50 mg per 100 g body weight resulted in a major decrease in the main testicular steroidogenic enzyme activity along with a low level of plasma testosterone and relative wet weight of sex organs, without any significant alteration in overall body development56.

 

Wound healing:

The effect of methanol extract administration ointment and injection of A. marmelos by topical and intraperitoneal route was examined in two forms of wound copies i.e. excision and incision wound models in rats57.

Anxiolytic and antidepressant activity:

This research aimed to assess the anxiolytic and antidepressant efficacy of A. marmelos methanol extract (MEAM) as well as its interaction with traditional antidepressant and anxiolytic drugs using an elevated maze and tail suspension tests in mice58.

 

Eye infection:

The leaves of A. marmelos gives effective management for ophthalmia as well as various eye inflammations (ex. Conjunctivitis)59.

 

Ear infection:

The A. marmelos root has astringent activity and is used as a home therapy for ear problems healing. The astringent extract of these roots combined with Neem extract (with antiseptic properties) helps to treat ear infection, chronic inflammation, and pus discharge. To treat ear infection leaf juice is stored in oil is frequently used as ear drops60.

 

Anti burn and radio protecting:

For the effective treatment of burn Bael fruit gum powder when mixed with mustard oil is used externally. It was concluded in various studies that because of free scavenging activity, the bael fruits shows a radioprotective effect.

 

Marketed formulations:

Some of the A. marmelos marketed formulations like tablets, syrups, capsules, etc. produced by different companies are listed below.

 

Table 7: Marketed formulations of A. marmelos

Marketed formulations

Company Name

Chyawanprash

Himalaya

A. Marmelos Capsulses

La-Medicca (India) Pvt. Limited

Leucare capsules

Shrey Nutraceuticals &Herbals

Entrostat Syrup

Ambika Medico

Kof-Rid Syrup

Ambika Medico

Pregeight

Sydler Remedies Pvt. Ltd.

Ojamin

Tates Remedies

Manasamithravatakram

Oushadhi

Pushyanugam gulika

Oushadhi

Vilwadigulika

Oushadhi

Ulco Bliss Tablets

Bliss Ayurveda

Capsule BilvGiri

Ayurvedic Sanjivani

R-Qunol Syrup

Vatsal Ayurvedic Products (P)ltd

 

Economical aspects of A. marmelos:

In light of background studies, novel and new herbal medicines still are required to treat diseases due to the high cost of synthetic medicines with some regular side effects. Herbal drugs are abundantly available as they are cheap and have small side effects. They have vast pharmacological and biological properties62. A. marmelos has curative properties including anti-diarrheal, laxative, antipyretic, analgesic, antimicrobial, anti-inflammatory, hypoglycemic, antioxidant, hepatoprotective, anti-cancer, cardio-protective, anti-spermatogenic, radio-protective, to treat peptic ulcer, to treat respiratory disorders, etc.4. Its photochemical studies have stated that this plant contains more than 100 essential chemical constituents responsible for its medicinal properties. Phytochemical studies on A. marmelos reported the presence of certain vital constituents like tannins, reducing sugar, phlobatannins, saponins, steroids, flavonoids, terpenoids, polyphenols, lignin, fat, oil, inulin, proteins, carbohydrates, cardiac glycosides, alkaloids responsible for its therapeutic value. Another study reported that protein, fiber, sugar, water, phosphorus, calcium, fat, iron, potassium, minerals, and vitamins (A, B1, B2, C) are present in fruit, which is a good source of energy and also has antioxidant activity63. Almost all parts including leaves, fruit, roots, and stem are used for therapeutic purposes. Nutritional drinks and Foods like dehydrated bael, fruit pulp, fruit squash, and RTS drink, jam, slab, bael powder, toffee, and panjiri is another product made from bael fruit27.

 

CONCLUSION:

Fast-growing populations, inadequate supply of medicines, side effects of many allopathic drugs, and ever-increasing resistance to current drugs for diseases are direct to the use of plant materials as a source of medicines for human beings. Historically, A. marmelos has been used for several ethnobotanical purposes. At present, A. marmelos has become an important source of medicine to cure various human and animal diseases. Apart from exploring possibilities for the preparation of generics drugs by the use of different plant parts of A. marmelos, the manufacture of the jam by the use of its fruit should be promoted as a health tonic on a commercial scale. Unfortunately, most of the compounds have not been adequately tested to discover lead molecules/pharmacophores. As a result, a thorough study is needed to establish the mechanisms of action as well as the bioactivity of the various phytochemicals and the efficacy of the medicinal values of A. marmelos. Besides, the pharmaceutical applications of different parts of A. marmelos are gaining much attraction from researchers. In the future, it would be an excellent pharmaceutical carrier for designing pharmaceutical dosage forms. Thus, shortly A. marmelos could be further misused as a source of useful phytochemicals compounds and can play a significant role in the modern system of medicine.

 

CONFLICT OF INTEREST:

None to declare.

 

REFERENCES:

1.      Verma S, Rani R, Vashishth E, Basu K, Pant P, Padhi M. Simple, Rapid and Precise Method for Quality Assessment of Different Parts of Aegle marmelos L. used in Indian System of Medicine. Research Journal of Pharmacognosy and Phytochemistry. 2013;5(5): 236-243.

2.      Mali SS, Dhumal RL, Havaldar VD, Shinde SS, Jadhav NY, Gaikwad BS. A Systematic Review on Aegle marmelos (Bael). Research Journal of Pharmacognosy and Phytochemistry. 2020;12(1): 31-36.

4.      Singh S. Standardization of processing technology of bael (Aegle marmelos Correa). In.: Chaudhary Charan Singh Haryana Agricultural University; Hisar; 2003.

5.      Agarwal V. Rural economics of medicinal plants: vegetation in the forests. Drug Plants of India. 1997;1: 1-6.

6.      Singh A, Sharma H, Kaushal P, Upadhyay A. Bael (Aegle marmelos Correa) products processing: A review. African J Food Sci. 2014;8: 204-215.

7.      Parichha S. Bael (Aegle marmelos): Nature's most natural medicinal fruit. Orissa Review. 2004;9: 16-17.

8.      Sharma PC, Bhatia V, Bansal N, Sharma A. A review on Bael tree. 2007.

9.      Meena AK, Sehgal H, Rao M, Panda P, Padhi M. Ayurvedic, Phytochemical and Pharmacological profile of Aegle marmeolus (Linn.) Corrae-A Review. Research Journal of Pharmacology and Pharmacodynamics. 2011;3(6): 340-344.

10.   Chadha K. Handbook of horticulture. Handbook of Horticulture. 2001.

11.   Neeraj VB, Johar V. Bael (Aegle marmelos) extraordinary species of India: a review. Int J Curr Microbiol App Sci. 2017;6(3): 1870-1887.

12.   Dhankhar S, Ruhil S, Balhara M, Dhankhar S, Chhillar A. Aegle marmelos (Linn.) Correa: A potential source of Phytomedicine. J Med Plant Res. 2011;5(9): 1497-1507.

13.   Sharma G, Dubey S. Medicinal values of Bael: A review. Int J Cur Pharm Rev Res. 2005;1(3): 20-31.

14.   Lambole V, Murti K, Kumar U, Bhatt S, Gajera V. Phytopharmacological properties of Aegle marmelos as a potential medicinal tree: an overview. Int J Pharm Sci Rev Res. 2010;5(2): 67-72.

15.   Orwa C. An Introduction to Aegle marmelos. Agro Data. 2009;4(2): 1-5.

16.   Purohit S, Vyas S. In: Aegle marmelos Correa ex Roxb, (Bael), Medicinal plant cultivation-A scientific approach. Agrobios, Jodhpur. 2004: 498-504.

17.   Shankar G, Garg K. Nutritional value of some important fruits. Handbook of Horticulture, Kitabistan, Allahabad. 1967: 37-41.

18.   Patkar A, Desai N, Ranage A, Kalekar K. A review on Aegle marmelos: a potential medicinal tree. International Research Journal of Pharmacy. 2012;3(8): 86-91.

19.   Charoensiddhi S, Anprung P. Bioactive compounds and volatile compounds of Thai bael fruit (Aegle marmelos (L.) Correa) as a valuable source for functional food ingredients. International food Research Journal. 2008;15(3): 287-295.

20.   Mandal PK, Mukherjee AK. Structural investigations on bael exudate gum. Carbohydrate Research. 1980;84(1): 147-159.

21.   Varshosaz J, Tavakoli N, Eram SA. Use of natural gums and cellulose derivatives in production of sustained release metoprolol tablets. Drug Delivery. 2006;13(2):113-119.

22.   Udeala O, Chukwu A. The binding property of mucuna gum in sulphadimidine and chloroquine phosphate tablets. Nigeria Journal of Pharmaceutical Sciences. 1985;1: 59-66.

23.   Olorunsola EO, Adedokun MO. Surface activity as basis for pharmaceutical applications of hydrocolloids: A review. Journal of Applied Pharmaceutical Science. 2014;4(10): 110-116.

24.   Vendruscolo CW, Ferrero C, Pineda EA, Silveira JL, Freitas RA, Jiménez-Castellanos MR, Bresolin TM. Physicochemical and mechanical characterization of galactomannan from Mimosa scabrella: Effect of drying method. Carbohydrate Polymers. 2009;76(1): 86-93.

25.   Patil D, Kulkarni A, Patil B. Fruit gum of Aegle marmelos as pharmaceutical aid. IJP-International Journal of Pharmacology. 2010;6(1): 68-71.

26.   Mahammed N, Gowda D, Deshpande RD, Thirumaleshwar S. Design of phosphated cross-linked microspheres of bael fruit gum as a biodegradable carrier. Archives of Pharmacal Research. 2015;38(1): 42-51.

27.   Chakraborty J, Dash S, Das B. Formulation and evaluation of controlled release mucoadhessive matrix tablets of levamisole: assement of purified fruit pulp polysaccharide isolated from aegle marmelos as mucoadhesive excipient. Asian J Pharm Clin Res. 2015;8(4): 262-269.

28.   Gurjar PS, Lal N, Gupta AK, Marboh ES. A Review on medicinal values and commercial utility of Bael. International Journal of Life-Sciences Scientific Research. 2015;1(1): 5-7.

29.   Alagumuthu G, Kirubha R. Biogenic Synthesis of Silver Nanoparticles using Aegle marmelos fruit extract and their Antibacterial potential. Asian Journal of Research in Chemistry. 2013;6(9): 839-844.

30.   Manjula A, Kumar PS. In vitro Evaluation of Biological Activity of Aegle marmelos (L.) Fruit. Research Journal of Pharmacy and Technology. 2016;9(4): 407-414.

31.   Ansary P. A hand book on the plant sources of indigenous drugs: International Book Distributors; 2005.

32.   Baliga MS, Bhat HP, Pereira MM, Mathias N, Venkatesh P. Radioprotective effects of Aegle marmelos (L.) Correa (Bael): a concise review. The Journal of Alternative and Complementary Medicine. 2010;16(10): 1109-1116.

33.   Jyothi KS, Rao BS. Antibacterial activity of extracts from Aegle marmelos against standard pathogenic bacterial strains. International Journal of Pharmtech Research. 2010; 2(3): 1824-1826.

34.   Mazumder R, Bhattacharya S, Mazumder A, Pattnaik A, Tiwary P, Chaudhary S. Antidiarrhoeal evaluation of Aegle marmelos (Correa) Linn. root extract. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2006;20(1): 82-84.

35.   Dhuley J. Investigation on the gastroprotective and antidiarrhoeal properties of Aegle marmelos unripe fruit extract. Hindustan Antibiotics Bulletin. 2003;45(1-4): 41-46.

36.   Tiku AB, Abraham SK, Kale RK. Eugenol as an in vivo radioprotective agent. Journal of Radiation Research. 2004;45(3): 435-440.

37.   Lampronti I, Martello D, Bianchi N, Borgatti M, Lambertini E, Piva R, Jabbar S, Choudhuri MSK, Khan MTH, Gambari R. In vitro antiproliferative effects on human tumor cell lines of extracts from the Bangladeshi medicinal plant Aegle marmelos Correa. Phytomedicine. 2003;10(4): 300-308.

38.   Agrawal A, Jahan S, Soyal D, Goyal E, Goyal PK. Amelioration of chemical-induced skin carcinogenesis by Aegle marmelos, an Indian medicinal plant, fruit extract. Integrative Cancer Therapies. 2012;11(3): 257-266.

39.   Rahman S, Parvin R. Therapeutic potential of Aegle marmelos (L.)-An overview. Asian Pacific Journal of Tropical Disease. 2014;4(1): 71-77.

40.   Vyas A, Bhargava S, Bhargava P, Shukla S, Pandey R, Bhadauria R. Evaluation of antipyretic potential of Aegle marmelos (L.) Correa leaves. Oriental Journal of Chemistry. 2011; 27(1): 253.

41.   Goel R, Maiti R, Manickam M, Ray A. Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa. Indian Journal of Experimental Biology. 1997;35(10): 1080-1083.

42.   Madhu C, Hindu K, Sudeepthi C, Maneela P, Reddy KV, Sree BB. Anti ulcer activity of aqueous extract of Aegle marmelos leaves on rats. Asian Journal of Pharmaceutical Research. 2012;2(4): 132-135.

43.   Ammar RB, Bouhlel I, Valenti K, Sghaier MB, Kilani S, Mariotte A-M, Dijoux-Franca M-G, Laporte F, Ghedira K, Chekir-Ghedira L. Transcriptional response of genes involved in cell defense system in human cells stressed by H2O2 and pre-treated with (Tunisian) Rhamnus alaternus extracts: Combination with polyphenolic compounds and classic in vitro assays. Chemico-Biological Interactions. 2007;168(3): 171-183.

44.   Singh S, Singh SK, Srivastava S, Singh P, Trivedi M, Shanker P, Dixit R, Rana RS. Experimental evaluation of diuretic activity of Aegle marmelos in rats. Int J Pharm Biol Sci. 2013;3(1): 98-102.

45.   Chauhan A, Agarwal M. Reversible changes in the antifertility induced by Aegle marmelos in male albino rats. Systems Biology in Reproductive Medicine. 2008;54(6): 240-246.

46.   Ruhil S, Balhara M, Dhankhar S, Chhillar A. Aegle marmelos (Linn.) Correa: A potential source of Phytomedicine. Journal of Medicinal Plants Research. 2011;5(9): 1497-1507.

47.   Rao CV, Ojha S, Amresh G, Mehrotra S, Pushpangadan P. Analgesic, antiinflammatory and antiulcerogenic activity of unripe fruits of Aegle marmelos. Acta Pharmaceutica Turcica. 2003;45: 85-91.

48.   Gupta N, Agrawal R, Shrivastava V, Roy A, Prasad P. In vitro Antioxidant activity and phytochemical screening of Aegle marmelos extracts. Research Journal of Pharmacognosy and Phytochemistry. 2012;4(2): 80-83.

49.   Urmi KF, Chowdhury AU, Diba F, Rahman KA, Habib R, Hamid K. Evaluation of Antioxidant and Cytotoxic Potential of Different Extracts from the Leaves of Aegle marmelos L. Research Journal of Pharmacy and Technology. 2013;6(4): 384-387.

50.   Pande KH, Salve PS, Rai RK, Bali NR, Wankhede HS. Investigation and In vivo Demonstration of Synergistic Antidiabetic activity of Aqueous Extract of Aegle marmelos and Withania coagulans. Research Journal of Pharmacology and Pharmacodynamics. 2014;6(2): 101-107.

51.   Upadhya S, Shanbhag KK, Suneetha G, Balachandra Naidu M, Upadhya S. A study of hypoglycemic and antioxidant activity of Aegle marmelos in alloxan induced diabetic rats. Indian J Physiol Pharmacol. 2004;48(4): 476-480.

52.   Sabu M, Kuttan R. Antidiabetic activity of Aegle marmelos and its relationship with its antioxidant properties. Indian Journal of Physiology and Pharmacology. 2004;48(1): 81-88.

53.   Prince PSM, Rajadurai M. Preventive effect of Aegle marmelos leaf extract on isoprenaline‐induced myocardial infarction in rats: biochemical evidence. Journal of Pharmacy and Pharmacology. 2005;57(10): 1353-1357.

54.   Singanan V, Singanan M, Begum H. The hepatoprotective effect of bael leaves (Aegle marmelos) in alcohol induced liver injury in albino rats. International Journal of Science & Technology. 2007;2(2): 83-92.

55.   Patel P, Asdaq SMB. Immunomodulatory activity of methanolic fruit extract of Aegle marmelos in experimental animals. Saudi Pharmaceutical Journal. 2010;18(3): 161-165.

56.   Kumar R, Kumar A, Prasal C, Dubey NK, Samant R. Insecticidal activity Aegle marmelos (L.) Correa essential oil against four stored grain insect pests. International Journal of Food Safety. 2008;10: 39-49.

57.   Kumar DU, Maiti R, Jana D, Ghosh D. Effect of aqueous extract of leaf of Aegle marmelos on testicular activities in rats. 2006.

58.   Jaswanth A, Loganathan V, Manimaran S. Wound healing activity of Aegle marmelos. Indian Journal of Pharmaceutical Sciences. 2001;63(1): 41.

59.   Kothari S, Minda M, Tonpay SD. Anxiolytic and antidepressant activities of methanol extract of Aegle marmelos leaves in mice. Indian J Physiol Pharmacol. 2010;54(4): 318-328.

60.   Sharma J, Painuli R, Gaur R. Plants used by the rural communities of district Shahjahanpur, Uttar Pradesh. 2010.

61.   Rusia K, Srivastava S. Antimicrobial activity of some Indian medicinal plants. Indian Journal of Pharmaceutical Sciences. 1988;50(1):57.

62.   Kruawan K, Kangsadalampai K. Antioxidant activity, phenolic compound contents and antimutagenic activity of some water extract of herbs. Thai J Pharm Sci. 2006;30: 28-35.

63.   Maity P, Hansda D, Bandyopadhyay U, Mishra DK. Biological activities of crude extracts and chemical constituents of Bael, Aegle Marmelos (L.) Corr. 2009.

64.   Yadav N, Singh P, Mehrotra R. Determination of some ethnomedicinally important constituents of Aegle marmelos fruit during different stages of ripening. Chinese Journal of Natural Medicines. 2011;9(3): 204-209.

 

 

 

Received on 01.01.2021            Modified on 09.02.2021           

Accepted on 13.03.2021   ©Asian Pharma Press All Right Reserved

Asian Journal of Pharmacy and Technology. 2021; 11(2):166-174.

DOI: 10.52711/2231-5713.2021.00028