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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2021 The   Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                        Review Article 

Aegle marmelos (L.) (Bael): A Systematic Review

Savita*, Ajeet Pal Singh, Amar Pal Singh

St. Soldier Institute of Pharmacy, Lidhran Campus, Behind NIT (R.E.C), Jalandhar-Amritsar by pass NH-1 Jalandhar-144011, Punjab, India

Introduction

Plants are particularly significant to humans since they contain various active ingredients that are the precursor for the creation of many drugs¹. For thousands of years, plants have been used in India as natural or herbal medicine. Plants used in Indian medicines are regarded as a rich source of numerous pharmacologically active principles and active ingredients, which are often employed in home treatments for a variety of diseases². Aegle marmelos (L.) Correa (A. marmelos), often well-known for Bael and belongs to the Rutaceae family, has been widely employed in indigenous systems of Indian medicine due to its many therapeutic characteristics³. A. marmelos leaves are presented to Lord Shiva, whose devotion would be incomplete without them.Shivadurme, or Shiva's tree, is another name for it. Ancient Indian texts such as the Yajurveda and the Mahabharata⁴.Bael includes a variety of phytochemicals such as alkaloids, tannins, essential oils, gums, resins, coumarin, and polysaccharide, which makes it effective for a variety of diseases. When compared to other fruits, it has a substantially higher nutritional value. It is also quite important in terms of the environment.

Synonyms⁵ 

Hindi (Bel, bael, sripal); Sanskrit (Bilva, sriphal, shivadruma, Shivapala); Telugu (Maredu); Bengali Cambodia (Phneou or pnoi); Vietnamese (Baunau); Malayan (M (Modjo). (Bel); Gujrati (Bil); Kannada (Bilpatra, kumbala, malura); Tamil (Kuvalum); Thai (Matum and mapin); 

Ecology ⁶ 

Bael is of Indian origin and can be found in Bangladesh, Egypt, Malaysia, Myanmar, Pakistan, Sri Lanka, and Thailand. The tree fills wild in dry woodlands on the slopes and fields of focal and southern India, just as in Burma, Pakistan, and Bangladesh, just as in blended deciduous and dry timberlands.

Botanical Description 

It is a slow growing medium to small size tree that can reach a height of 25 to 30 feet.The steam is soft and dense, with a few spiky branches. Table 1 contains the whole botanical description of A. marmelos⁷.

Table 1: Botanical Description of Aegle marmelos (L.)

Traditional utilization of Aegle marmelos

A. marmelos is extensively described in Vedic literature for the treatment of a variety of diseases.

It has long been used to cure a range of ailments^8-14, which are summarised in Table 2.

Table 2: Various parts of Aegle marmelos utilized

Biophysical limits ¹⁵

Bael is located at an elevation of 0-1200 meters; it requires an annual temperature range of 6 to 48 degrees Celsius and an annual rainfall range of 570 to 2000 millimetres. Furthermore, it demands well-drained soil and grows best in rocky soils and alkaline with pH levels ranging from 5 to 8.

Taxonomy ^{5, 16} 

Kingdom: Plantae

Order: Sapindales

Family: Rutaceae

Sub family: Aurantioideae

Genus: Aegle

Species: A. marmelos

Phytochemistry

A few investigations have been led to discover dynamic compound fixings from different areas of the bael plant^{2, 7, 17-18}.Table 5 lists the chemical compounds extracted from A. marmelos.

Table 3: Plant Part Chemical Constituents

Pharmacological studies

A. marmelos is one of the most frequently utilised medicinal and nutritional plants in the Rutaceae family. This plant has recently been found to have a variety of therapeutic benefits shown in Figure 1.

Figure 1: Pharmacological activities of A. marmelos

Wound Healing Activity

The impact of skin and intraperitonial organization of methanolic concentrates of Aegle marmelos balm and infusion on two sorts of twisted models in rodents, extraction and entry point, was explored. The infusion and salve of Aegle marmelos methanolic separate got critical reactions in both. As proven by an increment in elasticity in the entry point model, the concentrate helps in the mending cycle. The outcomes were likewise contrasted with those of the criticized drug nitrofurazone ^{7, 19}.

Antipyretic potential

A. marmelos' antipyretic movement on Brewer's yeast actuated pyrexia in pale skinned person rodents. They show that at portions of 200 mg/kg body weight and 400 mg/kg body weight, the ethanolic extricate created a critical (P0.001) decrease in high internal heat level in a dose subordinate way. The concentrates' antipyretic viability was similar to that of paracetamol (100 mg/kg body weight) ²⁰. 

Antidiarrhoeal activity

The antidiarrheal activity of a chloroform extract of A. marmelos root. In an in vitro research, the extract was found to be equivalent to ciprofloxacin and mostly active against Vibrio cholerae bacteria, followed by Escherichia coli (E. coli) and Shigella spp²¹. 

The antimalarial activity of alcoholic extracts of A. marmelos seeds and leaves was tested in vivo and in vitro against the Plasmodium berghei NK65 strain. The seeds were schizontocidal in both systems, while the leaves were solely schizontocidal in the in vitro system²².

Ulcer healing 

In albino rats, A. marmelos fruit pulp extract lowers mucosal thickness, superoxide dismutation, catalase activity, and glutathione levels considerably. Ulcer index, aspartate aminotransferase, alanine aminotransferase, and lipid peroxidation activity all increased significantly. These data suggest that an antioxidant mechanism may impact A. marmelos' gastroduodenal preventative and antiulcerogenic effects. ²³.

Diuretic activity

Several organic extracts and fractions of A. marmelos fruit were studied for their diuretic properties. The extracts were administered to the rats at dosages of 300, 400, and 500 mg/kg intraperitoneally.To examine the diuretic impact, they analysed urine volume and salt content in urine. They observed that the ethanolic extract generated a significant increase in sodium excretion at the higher dosage (500 mg/kg).Petroleum ether, chloroform, and ethyl acetate fractions are also effective ²⁴. 

Antithyroid activity 

Thyroid hormone levels were lowered when the leaves of A.marmelos were extracted. It was due to the presence of scopoletin, which has a stronger therapeutic effect than the propylthiouracil drug. ².

Immunomodulatory activity 

It was discovered that methanolic leaves extract of Aegle marmelos stimulate cell mediated and antibody mediated immune responses in rats. However, a low dose of methanolic extract of Aegle marmelos was found to be most effective in cell mediated immune response, whereas a high dose was found to be most effective in humoral immunity²⁵. 

Antifungal activity 

Essential oil from Aegle marmelos leaves may meddle with the Ca2+-dipicolonic corrosive metabolic pathway and maybe limit spore improvement, as per an examination. A.marmelos leaf removes in ethanol, methanol, and water showed antifungal adequacy against dermatophyte organism ²⁶. 

Antimicrobial activity 

It has been stated that A. marmelos has traditionally been used to treat a variety of infectious disorders by inhibiting a wide range of harmful microorganisms. The antibacterial activity of A. marmelos leaves and fruit extract was investigated. The use of leaf and fruit extracts against Roultella plantikola resulted in inhibition zones of 11 mm and 9 mm, respectively. The plant extract produced a maximum inhibition zone of (18mm) activity against the fungal strain Penicillium chrysogenum and a minimum inhibition zone of (7mm) activity against Candida albicans²⁷.

Antioxidant activity 

The DPPH radical scavenging method, the reducing power assay, the nitric oxide scavenging assay, the superoxide radical scavenging assay, the ABTS radical scavenging assay, and the H2O2 radical scavenging assay were used to determine the antioxidant activity of A. marmelos fruit pulp methanolic and aqueous extract. The antioxidant activity of both the aqueous and alcoholic extracts was high. Unripe fruit likewise showed a greater free radical inhibition percentage than ripe fruit. ²⁸. 

Radioprotective effect 

One of the most important cancer therapies, especially for those with critical visceral tumours, is radiotherapy. It has certain bad side effects, despite the fact that it is quite valuable all over the world. In mice exposed to various amounts of gamma radiation, the radioprotective effect of bael fruit hydroalcoholic extract was investigated. Before being subjected to 10 Gy 60Co gamma-rays, Swiss albino male mice were administered 5, 10, 15, 20, or 40 mg/kg Aegle marmelos extract intraperitoneally every day for 5 days. After 30 days of post-radiation therapy, the majority of survivors report maximum protection ²⁹. 

Contractile activity 

The contractile action of Aegle marmelos leaves alcoholic extract was discovered on guinea pig separated ileum and tracheal chain due to its traditional usage in treating asthma and associated disorders. The alcoholic extract of A. marmelos leaves at low and high dosages of 1 mg/ml and 2 mg/ml caused the guinea pig ileum and tracheal chain to relax the most owing to H1 receptor depression³⁰.

Antiarthritis activity 

The leaves of Aegle marmelos were found to be anti-collagen in Wistar albino rats, causing arthritis ³¹.

Analgesic activity 

Writhing and tail immersion tests were used to investigate the antinociceptive effect of A. marmelos leaves methanol extract in mice. The greatest possible impact of methanolic extract (200 mg/kg p.o.) was statistically significant when compared to other dosages. It is concluded that the methanol extract of A. marmelos leaves has a potent analgesic effect ³².

Cytoprotective effect 

This effect has been found in the freshwater fish Cyprinus carpio.For 1, 8, 16, and 32 days, experimental fish were maintained at sublethal metal ion concentrations. After 32 days, the fish were fed Aegle marmelos crude powder (500 mg/kg diet).By stabilising the plasma membrane and regulating the antioxidant enzyme system, the therapy produced a cytoprotective effect. ³³.

Anti-constipating effect 

The majority of the available ripe fruits are thought to be a natural remedy for various types of laxatives. The fruits of A. marmelos are commonly used to cleanse and tone the gut. Consuming this fruit on a regular basis for two to three months helps in the evacuation of old accumulated faecal matter from the colon. It is commonly consumed in the form of'sherbat,' which is formed from ripe fruit pulp³⁴.

Anticancer activity

The effects of Aegle marmelos fruit extract on breast cancer in rats generated by 7, 12-dimethylbenz(a )anthracene (DMBA). The study employed female Charles Foster rats that were 55–60 days old and weighed approximately (150 10 g). They were stimulated orally with DMBA (20 mg/mL diluted in Olive oil). The rats were given Aegle marmelos ethanolic fruit pulp extract (200 mg/kg b.w./day) orally for 5 weeks after developing breast tumours (approximately 0.5 cm) and the amount of tumour was assessed. Treatment with Aegle marmelos resulted in a substantial reduction in breast tumour volume (P 0.05), as well as a substantial drop (P 0.0001) in serum biomarkers such as TNF-, serum malondialdehyde (MDA), and glucose levels. In a rat model, the ethanolic fruit pulp extract has anti-proliferative effect by slowing the progression of breast cancers.³⁵

Transcriptome Analysis

The transcripts of A. marmelos were also annotated using information from other Rutaceae species, such as Citrus clementina and Citrus sinensis.482 transcripts were classified as cytochrome p450s (CYPs), whereas 314 transcripts were classified as glucosyltransferases (GTs).The monoterpenoid biosynthesis pathway found the most prevalent in A. marmelos leaves. A total of 133,616 contigs were assembled into 46,335 unigenes with lengths ranging from 201 to 14,853 bp.There were 7002 transcription factors and 94,479 SSR markers in the study³⁶. 

Antidiabetic activity

The circulatory alterations in alloxan-induced diabetic rats treated with Aegle marmelos methanolic leaf extracts. The study included five treatment groups of methanolic leaf extracts: control, diseased, low dosage (100mg/kg), medium dose (250mg/kg), and high dose (500mg/kg).Very-Low-Density Lipoprotein (VLDL), Serum Sialic Acid, Glutathione Peroxidase, Serum Catalase, Ascorbic acid, Sodium, Potassium, and Chloride levels were used to assess the cardiovascular effects. When compared to the sick treatment groups, the high dosage treatment group had significantly lower levels of Very Low-Density Lipoprotein (VLDL), Serum Sialic Acid, Glutathione Peroxidase, Serum Catalase, Ascorbic acid, Sodium, Potassium, and Chloride. When compared to the high dosage treatment group as well as the sick group, low and medium dosage treated animals exhibited no significant change in these cardiovascular parameters³⁷.

Food applications

The health advantages of bael are not confined to the edible section (fruit), but also include the non-edible portions (root, trunk, bark, leaf, blossom, and seed), which contain biologically active substances in equivalent amounts. With growing awareness of the importance of diet for human well-being among health-conscious consumers, interest in functional foods has grown. As a result, research into the functional attributes of various under utilised plants has been reaffirmed, and various sources have emerged as suitable food material for the processing industry. Several research publications gathered from diverse bibliometric sources showed that A. marmelos and its bioactive ingredients might play a key role in the prevention of oxidative stress-related chronic and degenerative disorders. The focus of this study is on contemporary scientific information on A. marmelos nutrition and bioactive profile, health benefits, clinical and nonclinical studies of various phytoconstituents, and A. marmelos potential in the food processing sector for diverse food items³⁸.

Conclusion

Several parts of A. marmelos have been classified as traditional healers, capable of curing a wide range of human ailments. There are several phytoconstituents in A. marmelos that are significant components in the plant's medicinal effectiveness. Almost every part of this plant is used to cure a variety of illnesses, including the leaf, fruit, seed, bark, and root. Given the Bael tree's great potential, it should either be cultivated or preserved in order to maximize its potential for exploitation and the discovery of new and effective herbal treatments. To produce goods for better economic and therapeutic usage, a comprehensive research and development effort should be undertaken. 

Disclosure Statement 

There are no conflicts of interest.

Acknowledgment

It’s our privilege to express profound sense of gratitude and cordial thanks to our respected chairman Mr. Anil Chopra, Vice Chairperson Ms. Sangeeta Chopra & Pro-Chairman Mr. Prince Chopra, St. Soldier Educational Society, Jalandhar for providing the necessary facilities to complete this work.

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