An overview of Betel vine ( Piper betle L.): Nutritional, pharmacological and economical promising natural reservoir

: With its magniﬁcent green heart­shaped leaf, the betel vine ( Piper betle L.) is also known as Paan in India. It is a member of the Piperaceae family. It is cultivated in the coastal regions of Odisha (Balasore, Jagatsinghpur, Puri, Khordha, and Ganjam). Paan is consumed by over 1 million people throughout the state, but they are unaware of its high nutritional quality. It is considered superior to pharmaceuticals and is one of the best remedies in nature. It has anti­microbial, anti­apoptotic, anti­cancer, antioxidant, and anti­inﬂammatory attributes. Furthermore, the leaves retain eugenol­rich essential oil (EO) (1­3%), which is the hotspot for medication, stimulants, antiseptics, tonics, and other ayurvedic compositions. This oil can also be used as an industrial raw material to make medications, fragrances, tonics, mouth fresheners, food additives, and other products. It contains anticarcinogens, which show potential


Introduction
The betel vine (Piper betle L.) belongs to the Piperaceae family, which also contains pepper and kava. Paan leaves are produced in the Philippines, Malaysia, India, Sri Lanka, Taiwan, Thailand, and other Southeast Asian countries as a postmeal mouth freshener. It is primarily consumed in South Asia and by certain Asian emigrants worldwide as betel quid or paan, in combination with areca nut or tobacco (Saraswat et al., 2020;Shah et al., 2021). A sheaf of betel leaves is typically presented in Odisha as a token of respect and auspicious beginnings in traditional culture. It belongs to the genus Piper of the Division Magnoliphyta, Class Magnolipsida, Order Piperales, and Family Piperaceae. It is a unisexual perennial evergreen climber with shiny cardio leaves and white catkins that bloom in the spring. Betel vine is catego rized into odorous and nonpungent kinds depending on the form, length, and flavour of the leaf. The plant's leaves are basic and have an acuminated crown. Mostly, the leaves are smooth and shining. The leaves differ in color from light green to dark green. The leaves are longstalked with 23 pairs of secondary veins (Swapna et al., 2012). The betel plant's limbs usually bulge at the nodes and are com pletely smooth. Female spikes are cylindrical, where as male spikes are pendulous. Female spikes measure 2.55.0 cm in length. In the humid environment of East India, female plants often generate blooms or fruit (Sengupta and Banik, 2013;Rahman et al., 2020).
Throughout thousands of years, nature has pro vided a reservoir of medical substances, and current medications are derived from ecological resources. The betel leaves contain a variety of bioactive com pounds and are employed in ancient medical meth ods. Such leaves are high in minerals, vitamins, enzymes, proteins, and essential oil (EO), and they are very nutritious (Nayaka et al., 2021;Paswan et al., 2021). They also include certain useful therapeu tic components for the therapy of disorders of the brain, liver, and cardiac Ullah et al., 2020). Polyphenols, alkaloids, steroids, saponins, and tannins were also found. In the Indian subcontinent, medicinal plants are a resource of eco nomical worth (Sen and Chakraborty, 2017; Madhumita et al., 2020). Medicinal plants are the pri mary source of medicine for the bulk of the rural community in emerging nations, and consequently play a key role in their health systems (Patra et al., 2014;WHO, 2019). Upto 80% of people in developing countries still use local medicinal herbs for their basic health care needs (Sen and Chakraborty, 2017;WHO, 2019). Furthermore, diastase and catalase activities are detected in the leaflets (Abrahimet al., 2012;Shah et al., 2021). It assists in curing and treating many conditions, including halitosis, boiling and absceeding, conjunctivitis, headache, constipat ion, hysteria, itching, mastitis, leucorrhoea, otor rhoea, mastoiditis, gum swelling, ringworm, rheuma tism, abrasions, injuries, cuts, etc (Shukla et al., 2018). Because of their antibacterial and antioxidant properties, these oils have a promising future in the novel food packaging industry (EI Asbahani et al., 2015;Guha and Nandi, 2019;Nguyen et al., 2021), as well as being a prospective and appealing flavouring component for the food and beverage sectors.
This plant is grown as a cash crop in the Balasore, Jagatsinghpur, Puri, Khordha, and Ganjam areas of coastal Odisha (Jena, 2021). In Assamese/Urdu/ Hindi/Odia/Bengali, the betel leaf is recognised as Paan, whereas in Sanskrit it is considered as Taambuul and Nagavalli. The finest betel leaf is the "Magadhi" type cultivated near Patna in Bihar, India. The popular type of betel leaf in Kerala is called "Venmony Vettila" and comes from Venmony near Chengannur (Guha and Nandi, 2019). In Odisha, four distinct forms of betel leaf are grown. The Bhograi block in the Balasore district is known throughout the country for its betel vine farming (Patra and Pradhan, 2018). Cultivars with the prefix Desi in their names, on the other hand, always relate to the cultivars Desavari in Madhya Pradesh, Kapoori in Maharashtra, Bangla in West Bengal (Guha and Nandi, 2019), Bali and Chandrakana in Bhogarai ( Fig.  1 A1A2, B1B2). The varieties are Nova Cuttak, GodiBangala ( Fig. 1 C1C2), Sanchi ( Fig. 1 D1D2), and Birkoli. Only one type, GodiBangala, is grown by the locals in the research region Bhainchigodi (Patra and Pradhan, 2018). Odisha is one of the states that pro duce the most betel vine. In the context of such sci entific research, this review article tries to summarise all the possible information on betel leaf with its propagation, socioeconomics, and bioactive com pounds, justifying wider possibilities for its use as a natural source for people in Coastal Odisha.

Habitat and Ecology
Betel vine is primarily grown in Odisha's coastal districts such as Balasore, Jagatsinghpur, Puri, Khordha, and Ganjam (Jena, 2021). All the respective district locations are as follows. 20. 27°N and 86.17°E, 19.48°N and 85.48°E, 20.18°N and 85.62°E, 19.38°N and 85.05°E (Fig. 2). NorthWestern highlands, the inner alluvial plain, and the coastal belt are the three geographical regions that can be found in all five dis tricts. Those regions are flooded with brackish water from estuarine rivers, making them unsuited for agri culture in a regular manner. Those lands are current ly used for betel and coconut agriculture (Ahuja and Ahuja, 2011). Recently, prawn culture and salt pro duction units have sprouted in this region. Paddy, fish, and betel vine farming are important parts of the local economy in these districts. The soil in the central zone is mostly sandy loam and clay loam, making it perfect for producing rice and betel vines (Kaleeswari and Sridhar 2013). Coastal Odisha has an oceanic climate and experiences rainfall from the southwest monsoon (Gouda et al., 2017). The coast line area has a pleasant temperature. The summers in such districts are hot, having excessive humidity during the monsoon season, a dry winter, and little diurnal temperature fluctuation over the year (Krishnan et al., 2020). The district's average annual precipitation is 1591 mm, which is over 9% greater than Odisha's average. Tropical cyclones, which bring a lot of rain to the area, are responsible. Due to the district's proximity to the Bay of Bengal, cyclones are common. Cyclones, which begin in the Bay of Bengal over the Andaman and Nicobar Islands and proceed towards India's east coast, are a common occurrence in the district (Sahoo and Bhaskaran, 2016). The SouthWest monsoon brings more than 70.9% of the annual precipitation from June to September. The three distinct seasons observed in the area are sum mer (MarchJune), rainy (JulyOctober), and winter (NovemberFebruary) (IMD, 2020).

Cultivation and propagation in coastal Odisha
This plant's cultivation needs consistent soil wet ness, adequate humidity, and moderate heat, which are not usually present in the ecological environment (Filipovic, 2020). Variations in these environmental variables were found to be harmful to the plant. As a result, it is grown in an artificially manufactured hut like structure that keeps the plant's growth parame ters within a reasonable range, simulating natural ecological conditions (Raza et al., 2019). The building is known as a 'Baraja,' and is made up of various plant materials like (Bambusa vulgaris Sch. ex Wendl.) and Bamboo stems (Bambusa bambos L. Voss.), jute (Corchorus capsularis L.), paddy straw (Oryza sativa L.) (Fig. 3 AB), Khadi or Chaee stick, and coconut leaves (Cocos nucifera L.) make up the Baraja architecture (Arunda donox L.) (Haider et al., 2013). The structure's proportions are limited to 2 to 3m in height, 10 to 20 m in length, and 5 to 15 m in breadth. The plant is grown through vegetative pro liferation from cuttings of 3 to 5yearold vines. Plantlets with one or two nodes and connected leaves are commonly used as propagating specimens. The planting season varies depending on the area to area. It takes roughly a month for roots to develop and grow after planting. Plants are supported when  Hridayam," "Bhabaprakasha," "Harivamsa," "Varahapurana," and "Panchatantra and Jataka Stories" are among the Sanskrit writings that allude to it as "tamabool" (Kumar, 1999 Vernekar and Vijayalaxmi, 2019). After dehydration, the betel leaf samples became a concentrated source of nutrients, accord ing to the results of the nutritional analysis. The find ings support those of (Subhash and Neeha, 2014), who found that after sun drying and cabinet drying, the leaves preserved high levels of protein, fibre, and calcium. The moisture material of dehydrated betel leaves flour was 9.45%, fat 1.10%, protein 3.30%, ash 6.87%, carbohydrate 63.92%, fiber 10.15%, vitamin C, calcium, and iron were 1.11%, 2.57%, and 1.53% (Chauhan and Aishwarya, 2016;Akshata et al., 2018).

Phytochemicals found in betel leaf
The phytochemicals screening was analyzed on the ethyl alcohol extract of betel vine using standard protocol for identification of the constituents. The leaf extracts have various pharmacological activities which are prepared by using different solvents such as aqueous, ethanol, powder, and hot water (Kumari and Rao, 2015) ( Table 1 and Table 2). By this analysis, it was concluded that it consists of Tannins, Anthraquinones, Flavanoids, Alkaloids, Terpenoids, they have 57 leaves. After one year of plating, har vesting begins by plucking the leaves. The harvests are known locally as Maghei paan, Jhanji paan, Vejua paan, Nua paan, and Jagannath paan. Nua paan is harvested during the months of February and April. Cultivators remove dry or damaged leaves during this plucking period. Jhanji paan is harvested between May and midJuly. This is the season with the highest yield. Cultivators are removing some broken Khadi or Chaee sticks this season. During the months of August and September, Jagannath paan is collected. Farmers strategically gather the leaves from the low est section of the branches during this plucking. During the months of October and November, Vejua paan is collected. Cultivators pick the tops of branch es in this plucking technique. Maghei paan harvesting begins in December and continues until February (Patra and Pradhan, 2018). All total leaves are plucked in this collection. Farmers sprinkle water on leaves and use cotton sheets or paddy straw to keep them fresh. A "Pono" is made up of eighty paan leaves. After that, the leaves are distributed in local markets or transferred to other towns (Haider et al., 2013).

Pharmacological activities
Paan is healthy and significant because of its med ical, religious and ceremonial history (Rai et al., 2011). Asthma is also prevented, vocalisation is improved, and gums are strengthened. Indigestion, constipation, congestion, cough, and asthma are treated (Peddapalli et al., 2020). The antialzheimer bioactive compounds were found in various varieties of betel vine (De et al., 2021). The following bio chemical roles of phytochemicals from leaves are depicted in figure 5.

Possible source of wound healing agents
Betel vine component at 0.025 ml/l concentra tions boosted fibroblast reproduction and encour aged umbilical cordmesenchymal stem cells (UC MSCs) proliferation at 0.03 ml/l, increasing in vitro model wound healing in accordance with empirical evidence. The homogenate reduces the presence in cells of oxidative stress factors such as VCAM, CD248, and IL33, so that recovery of umbilical cord cells can be accelerated (Thi et al., 2021). Researchers discov ered that natural lysates of leaves containing pheno lic compounds can reduce the activity of inflammato ry factors and oxidative stress, which could be useful in regenerative medicine.

Insecticidal activity
The crucial oil extracted from the sheets of betel vine was examined on the corn weevil (Callosobruchus maculatus F.) and the beetle (Sitophilus zeamais M.) and has been suggested as a potential crop protective agent (Nair and Kavrekar, 2017). Piperaceae EO has been extensively researched for its larvicidal role in mosquito larvae control (Huong et al., 2019;Alves et al., 2021). Piper permucronatum, Piper arboreum, Piper gaudichaudianum, Piper marginatum, Piper longum, Piper humaytanum, and Piper aduncum EO have the ability to regulate Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus (Santana et al., 2015;Takeara et al., 2017;Silva et al., 2019;Durofil et al., 2021). Piper aduncum was found to be larvicidal, killing Aedes aegypti mosquito larvae at concentrations of 500 and 1000 ppm (Oliveira et al., 2013;Martianasari and Hamid, 2019).Within a few days of being exposed to similar amounts of Piper marginatum EO, 100% of Aedes aegypti larvae died (Santana et al., 2015;Marques and Kaplan, 2015). The EO of betel vine has regulated the population as well as various stages of mosquito (Aedes aegypti) and acts as an alternative bioinsecticide (Martianasari and Hamid, 2019).

Antimicrobial activity
The antibacterial properties of the EO obtained from the leaves are impressive (Prasetya et al., 2021). They prevent bacteria from adhering to initial tooth plaque (Punuri et al., 2012). The antifungal activities of magahi variant betel leaf EO were inves tigated by (Madhumita et al., 2019;Madhumita et al., 2020). Towards Aspergillus flavus, the minimum level of EO inhibition (MIC) from leaves was found to be 0.8 ml/l Chavicol, allylpyrocatechol diacetate, chavibetol acetate, propenylphenols, hydroxychavi col, and chavibetol are some of the aromatic com pounds discovered in the chloroform extracts (Aliahmat et al., 2012). Antibacterial properties against Proteus vulgaris, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes   (Hartini et al., 2018). The model influence of betel leaf EO of 'Meetha' was explored by (Basak, 2018) on the Aspergillus flavus germination period and the population spore of Penicillium.
Antigiardial assay Giardiasis is regarded by humans worldwide as the most frequent protozoan diarrheal illness. Researchers have sought out novel, herbal medicines that might replace commercial pharmaceuticals with unpleasant potential side effects in the treatment of giardia (Nazer et al., 2019). The betel vine extracts Antidiabetic activity More troublingly, the increase in the incidence of diabetes has an impact not only on advanced coun tries but also on emerging nations that have less money to deal with another serious illness burden again. Present diabetes therapies can have side effects, so the move now to herbal remedies is more effective, cheaper, less risky, and less side effective. The present information reveals that the juice of the betel vine has assurance for antidia betes. Betel vine leaves have been examined in induced diabetes rats (CEE), normoglycaemic, and strepozotocin (STZ) with antidiabetic action assessed by oral hot water and ethanol extract (HWE) (Khatun et al., 2016;Arawwawala et al., 2011). Blood glucose levels were dosedependent in both HWE and CEE in normoglycaemic rats. During the glucose tolerance process, both extracts consid erably lower the external glucose load. HWE has an antidiabetic action comparable to CEE. Both extracts have not been harmful and tolerated since pro longed oral administration (No open evidence of renotoxicity, and hepatotoxicity). Moreover, the weight of the spleen was increased in treated groups, indicating lymph regenerative effects (Khatun et al., 2016). Betel leaf extraction is a useful antidiabetic feature that enables blood sugar levels to be regulated. This investigation discovered betel vine extracts lowering the blood glucose level by the activation of insulin/biomimetic action and have a possible therapy for type2 diabetic patients (Arawwawala et al., 2011) ( Table 2). Increased transaminase activity (SGPT and SGOT) has been found in several investigations in liver and serum diabetic rats (Ramachandran et al., 2012).

Gastroprotective activity
Extraction of betel vine was also found to be mediated gastro defensive activity, resulting in (i) an increase in the production of mucus and/or bicarbon ate, (ii) a decrease in the amount of stomach acid secreted, or (iii) a decrease in gastric acidity ( Table 2). The antiulcerogenic properties of these compounds were also shown by their proteinprone and blood pressure effects. Powerful gastroprotective behaviors were demonstrated (Berenguer et al., 2006). Thus, the gastroprotective effect can also be influenced by secondary metabolites, such as alkaloids, saponins, tannin, flavonoids, and other phenolic compounds (Barbosa et al., 2019).

Anti-asthmatic effect
Betel vine's antioxidant, antiinflammatory, and antihistamine activity have been linked to a wide range of diseases Aara et al., 2020;Ahmed et al., 2021;ClemenPascual et al., 2022). The antiasthmatic activity of betel vine in guinea pigs has been tested . Asthma is the tra cheobronchial smooth muscle's hyper reactance to a multitude of stimuli (Chapman and Irvin, 2015). Bronchitis is a chronic inflammatory disease. Bronchial asthma may be caused by free radicals and superoxide (Phaniendra et al., 2015;Boukhenouna et al., 2018). Histamine has the potential to produce bronchoconstriction (Yamauchi and Ogasawara, 2019). The extract can substantially minimize the impact of bronchial asthma, but it has fewer effects than diphenylhydramine. But other mediators such as leukotriene play a vital part in asthma in humans. Betel vine has been reported to have the ability to reduce bronchial asthma in guinea pigs, despite its weak influence on human asthma (Darvhekar et al., 2011;Misra et al., 2014;Rekha et al., 2014;Ahmad et al., 2021).

Role of betel leaf extract in thyroid disease
Ethylacetate Piper betle L. (EPBL) extract adminis tration reverted the T4induced rise in serum thyroid hormones, heli marker enzymes, MDA, and LOOH, but improved antioxidant enzyme activity and decreased the content of glutathione. Lighter results from liver histology show that the EPBL administra tion has enhanced twisted hepatic tissue architecture in hyperthyroid species. Analysis of the massspec troscopy of highresolution liquid chromatography showed the presence of four primary glycosides, including quercetine, rutin, kaempferol, and luteo line. The antithyroidism of EPBL was seen to be caused by hyperthyroidism induced by T4. EPBL's antithyroid and antioxidant properties may be attributable to the existence of extracted flavonoid glycosides in hyperthyroid animals which may have blocked the secretion of the thyroid hormone and translation of T4 into T3 by 5'DI inhibitors (Panda et al., 2018).

Anticancer activity
Anticancer agents with antioxidant activities may provide their beneficial effects by balancing ROS, such that cancer cells do not proliferate when apop tosis is not allowed to occur (Abrahim et al., 2012). Chronic inflammation is the root cause of many human diseases, including cancer and tumors, according to experimental and clinical research (Kangralkar and Kulkarni, 2013). The betel leaf was used for irritation in the mouth cavity as a typical folk medication. Mouth cancer is among the ten most common cancers, with 90% of cases occurring in Southeast Asia, where cigarette and smoking behav iors are common (Jiang et al., 2019). One of the earli est studies (Toprani and Patel, 2013) discovered that topical treatment with leaf extracts inhibited pineneinduced oral cancer in hamsters. It was also discovered that combining leaf extracts and turmeric into the dietary supplements was beneficial. Curcuma manga, Dendrophthoe pentandra, Piper betle L., and Catharanthus roseus extracts in breast cancer cell lines were explored as anticancer and radical free scavenging power (Widowati et al., 2013;Rekha et al., 2014). Betel vine has reported cancer preventative effects (Kudva et al., 2018;Shukla et al., 2018;Malkani et al., 2021;Chowdhury and Markus, 2022). Supplementing leaf extract with potable water significantly reduced the concentration of benzo (a) pyreneinduced neoplasia of the forestomach. The leaf extracts contain antiproliferative and preventa tive chemical potential and can thus be utilized to treat several conditions, including human lung cancer (Banerjee and Shah, 2014).

Cardioprotective action
Acute myocardial infarction is caused by an imbal ance between raised oxygen demand and decreased blood supply caused by prolonged ischemia (Smilowitz et al., 2015). During ischemia, the heart is further damaged by the formation of ROS. As a result, increasing antioxidant levels may help to pre vent future infarction (Munzel et al., 2017;Zhou et al., 2018). Pretreatment with betel vine enhanced hemodynamic and ventricular function parameters in rats with isoproterenol (ISP)induced myocardial infarction. It restored SOD, CAT, GSH, and GPx levels, decreased lipid peroxidation of the heart, and there fore lowered CKMB isoenzyme and LDH leakage into the blood (Arya et al., 2010). Platelet hyperactivity, which leads to intravascular thrombosis, is a key component in the development of cardiovascular dis orders (Kaur et al., 2018;Alkarithi et al., 2021).

Anti-malaria activity
As compared to the wellknown insect deterrent citronella oil, EO provided greater resistance against mosquito bites from Anopheles stephensi and Culex fatigans (Johirul et al., 2016). The oil provided greater than 4h of resistance from Anopheles stephensi and Culex fatigans when sprinkled at a rate of 20l/cm 2 , whereas citronella oil provided only 2.2 and 2.6h of protection, correspondingly. As a result, the power of paan to resist mosquitos has been established (Pal and Chandrashekar, 2010;Ibrahim et al., 2017;Cang et al., 2020).

Antioxidant activity
Many researchers have investigated the antioxi dant activity of extracts using a variety of solvents and extraction times (Alam et al., 2012;Aliahmat et al., 2012). The properties of the leaf extracts from various solvents were determined using highperfor mance liquid chromatography to calculate the oil water partition coefficient (HPLC). Due to their high oilwater partition coefficient, leaf phenolics have been shown to be less polar than other phenolic antioxidants. The investigation showed that the sol vent extraction and the period for preparing betel leaf extract (petroleum ether, methanol, water, and ethyl acetate) for use as a natural antioxidant are crucial acts against four different harmful bacteria, such as Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, and Proteus vulgaris, have been investigated by Chakraborty and Shah (2011), Lubis and Marlisa (2020) Nayaka et al. (2021), andNguyen et al. (2021). Others were isolated from these extracts, with few recognized and unknown metabolites. Various analytical methods such as NMR, Mass Spectroscopy, and IR Spectroscopy have been used for structural investigation. TBARS and DPPH methods conducted antioxidative investiga tions. Abdullah et al. (2015) found antioxidant betel vine extract activity and its components. 11 diphenyl2picrylhydrazyl (DPPH) demonstrated that the Bangla variety of betel vine is the best antioxi dant that can be combined with total phenol con tents and lower the strength of these respective extracts in a test for ethanol extracts of three vari eties (Bangla, Sweet, and Mysore) of Piper betle L. (Swapnil et al., 2014;Sarma et al., 2018). Bangla extract column chromatography resulted in chavi betol (CHV), allylpyrocatechol (APC) separation, and corresponding glucosides. Similar chemical character istics of three Piper betles were identified after HPLC analysis (Abdullah et al., 2015).

Marketing and socioeconomic status
Around 15 to 20 million Indians regularly eat betel leaves, and there are an estimated 2 billion betel leaf consumers worldwide, proving the crop's enormous economic potential (Jeng et al., 2002). As for national employment generation, an estimated 15million peo ple in India depend on betel leaf production, process ing, handling, transportation, and selling as a source of income (Jana, 1995). It has been reported that these varieties of betel leaf, such as Nova Cuttak, Godi Bangala, Sanchi, and Birkoli, are grown in coastal Odisha. Barajas' construction, annual mainte nance, leasing costs, and input costs like labor and fertilizers are included in the cost of betel leaf pro duction, which are essential for their crop propaga tion. Throughout the observation phase, each sea sonal and annual money expenditure in a Barajas in coastal Odisha was examined. Patra and Pradhan (2018) reported that US$ 474.20 and $ 596.70 were invested for watering and irrigation for one year. However, it is too costly for a cultivator. As a result, some cultivators are unable to hire labor and must rely on their own manpower to irrigate their crops. As a result, they are no longer charged for watering labor, and their annual financial investment is merely $ 122.50. As a result, excluding irrigation and water ing costs, the cultivator paid $ 21.00, $ 21.08, $ 51.37, and $ 7.90 for each harvesting in a year. Cultivators have spent a lot of money on their tradi tional agriculture in the hopes of getting a high return on their investment from the local market. However, the area is wellknown for its betel vine agriculture, and the market price is quite low. As a result, growers sell their crops through a middleman. Thus, Cultivators can earn money from two different sources. Paan's annual income from the local market is $ 131.72, with a middleman fee of $ 172.92, and income from the local market per harvesting is $ 16.47, $ 24.70, $ 32.93, $ 32.93, and $ 24.70. Annual market prices varied depending on the purity of the paan. The local market rate was higher in the winter season, at $ 32.93, in the rainy season, at $ 24.70, and in the summer season, at $ 16.47, i.e. cheaper in all seasons. People worked 360 days a year in a paan Baraja, plus 26 days of minor work within the Baraja. Laborers take five vacations each year, all of which are selfinitiated. Its economic operations are now restricted to the local and national levels (Patra and Pradhan, 2018). In tropical nations, cash crops such as cocoa, cola nuts, coffee, citrus fruits, and other highincomegenerating crops were more highly val ued than the production of betel vine. Several unidentified infections and insects harm betel vine cultivation, resulting in significant losses for growers (Vishwakarma and Purohit, 2020). Another issue is seedling transportation. It happens when seedlings are damaged. Transportation, too many middlemen, a lack of grading, price fluctuations, and a lack of financial resources were all issues in marketing. The intensity of pests and illnesses, lack of water, soil quality, and the frequency of rains and winds were all agrobiological issues that limited productivity (Bar et al., 2020). The primary reasons for the low betel leaf output are conventionally handled operations, uned ucated laborer, and inferior planting materials.

Foot Rot
Phytophthora spp. causes the most common fun gal illness. The plantation suffers from foot rot (Haider et al., 2013;Meszka and Michalecka, 2016). Phytophthora species was discovered in 1927, which was eventually recognised as P. nicotianae var. para sitica (Meng et al., 2014). Foot rot induced by P. parasitica and Phythium vexans de Bery (Phythium piperinum Dastur) was documented by (Haider et al., 2013). The lamina of the leaves begins to drop gradu ally, while the petiole remains upright. This sickness is known in the area as 'Khada Kala', 'Khada Pacha', or 'Madua'. Local growers are spraying Blitox and Tegron drugs to avoid the sickness from spreading (Haider et al., 2013). Sclerotium rolfsii causes foot and root rot which is the most devastating disease that decreases the production of betel leaf (Rahman et al., 2021).

Leaf spot
Patra and Pradhan (2018) reported a leaf spot dis ease induced by Fusarium semitectum. Berk. et Rav. Singh and Shanker (1971) described infections induced by Cladosporium pipericola, Drechslera rostrata, Corynespora cassicola, and Cercospora piperisbetle in Madhya Pradesh and Uttar Pradesh, India (Maiti and Sen, 1979). The sickness is called "Champa Fulia" or "Champa Tipa" in the area. The leaves' tips are tiny and curling. Farmers must cut sick leaves as soon as they are spotted, or the virus may migrate to the main stem of betel vines in a few days. It was also carried by ants and insects from one vine to another. This disease is more prevalent during the wet season. Farmers apply DiethenM 45 and urea water to these diseases to eradicate them (Maiti and Sen, 1979).

Powdery mildew
In India, the disorder was discovered in Mysore by Narasimhan in 1933. Oidium piperis Uppal is the major cause of powdery mildew disease (Park et al., 2012). This ailment is referred to as 'Jhalma' in the local community. On the bottom of the leaves, the infection appears as white to light brown powdery patches. At this phase, little white and black particles can be seen in the upper and lower regions of the leaves. This is a very communicable disease. There is no way to prevent or treat this illness. Farmers use a combination of dried fruit dust and Neem tree (Azadirachta indica A. Juss.) leaf juice mixed with water to dust betel vine leaves (Patra and Pradhan, 2018).

Collar rot
Sclerotium rolfsii Sacc., is a soilborne fungus, infecting the collar and root parts of various crops, its growth, development, and pathogenicity were dependent on environmental factors like tempera ture, relative humidity, and rainfall (Garibaldi et al., 2013). It is confirmed that S. rolfsii caused collar rot disease in betel vine which is reported to Garain et al. (2021) and cause 17100% crop loss in West Bengal.
One hundred twenty million kg of EO is produced globally from approximately 300 crops, which are worth about $4 billion, including 4% production from India (Shukla, 2015). The EO extracted from coastal areas of Odisha and obtained from different varieties such as Chandrakala (0.42%), Godi Bangla (0.37%), Balia (0.35%), Desibangla (0.32%), Maghai (0.30%), Dandabalunga (0.20%), Nahua (0.15%), and Karpada (0.15%) (Das et al., 2016). The leaves have indispens able oils which are known for their antiallergic, anti cancer, insecticidal, antibacterial, and antioxidant properties (Seow et al., 2014), making them healthy food preservatives with significant customer interest. The application of an alternative food preservative to prevent microbial spoiling is necessitated by the growing customer desire for natural products (Mandal et al., 2014;Roy and Guha, 2021). Besides being possible natural food preservatives, these oils could also have a future in novel food packets due to their antibacterial and antioxidant properties (EI Asbahani et al., 2015;Roy and Guha, 2021), as well as being a viable and appealing flavoring component for the food and beverage sectors. The EO ingredients added in ice cream, chocolate, suji halwa, cupcake, lozenge, rosogolla, etc. (Guha and Nandi, 2019). Basak (2018) reported that the EO of betel vine (var. Tamluk Mitha) has many potentials as a natural preservative in the food sector due to its safety and antimicrobial effectivity without affecting the sensory qualities of the food products. As a result, around Rs 3040 million worth of leaves are sold to nations like Italy, Great Britain, Bahrain, Hong Kong, Pakistan, Canada, Kuwait, Saudi Arabia, Nepal, and many other European countries each year (Pandey et al., 2018). Clearly, this shows the crop's ability to generate for eign money, which should be enhanced in the nation al interest. Export policy decisions may be modified to increase betel leaf exports, in addition to an ade quate study on export systems and intelligence. Rural and urban populations are increasingly using the plant for culinary and ethnomedicinal purposes, which has led to an increase in demand. Cultivation and preservation of betel vine in rural areas should receive renewed attention in order to prevent the extinction of these species and to provide economic benefits to rural populations.

Future studies
The leaves are frequently used as remedies because they contain important bioactive compo nents. Due to their inexpensive cost and ease of usage, they are widely utilized in India and abroad. To cure alcoholism, bronchitis, asthma, leprosy, and dyspepsia, it can be taken as a dietary additive or taken separately (Peddapalli et al., 2020). Because betel leaves decompose quickly, they cannot be pre served for long periods of time. As a result, extra leaves are dumped aside or sold as cow feed in the marketplace. In this scenario, improved research approaches should be used to extend the shelf life of leaves. Usually, several diseases and insects attack the betel vine throughout production, causing signifi cant losses to the growers. Microbes, parasites, and other contaminants can readily contaminate the leaves during preservation and transit. As a result, garbage utilization in the manufacturing industry is one of the most significant and difficult occupations on the globe. There are only a limited number of studies on the use of leaf isolates and EO. Because there is a dearth of study in this field, we should con centrate on its possible technologies in a variety of procedures such as food applications, pharmaceutical industries, cosmetic industries, and so on. Betel leaf postharvest damages can be reduced by using supe rior storage techniques. The functioning of each unit (manufacturing, processing, packaging, handling, transportation, and marketing) of betel leaves affects the majority of individuals directly or indirectly.
Based on the foregoing, the federal and state gov ernments should collaborate more effectively to fund diverse initiatives. A Research and Development Board should also be established by the government. This could help keep the price of betel leaves stable. This also aids in the expansion of cultivation and exportoriented operations, the development of con servation methods, and the reduction of waste and by outflow, among other things. If farmers, scientists, technicians, and researchers work together to resolve the limits, the economy and job prospects will grow.

Conclusions
This review article looked at the cultivation, nutri tional components, pharmaceuticals compounds, pharmacological activities, antimicrobial compounds, diseases, and economy. Betel vine has ample of vari ous metabolites such as phenolic tannins, anthraquinones, flavanoids, alkaloids, terpenoids, saponins, caediac possess more number of pharmaco logical activities and responsible for health benefits. As a result, there is a rising demand for using betel leaf extract and EO in a variety of industrial uses, including food supplements, cosmetics, and pharma ceuticals. Therefore, farmers of coastal Odisha have completely depended on the economy of betel vine cultivation and marketing at the national and interna tional level. Sometimes, the betel vine is plagued by many diseases during cultivation, which generates a huge loss for farmers. The betel vine production was devastated due to being infected with several fungal pathogens resulting in foot rot, leaf spot, powdery mildew, and collar rot. In addition, this study discuss es the recently accepted extraction technologies and characterization, both of which are critical for the growth of the product's economic worth. Bioactive chemicals from betel vine should be isolated, extract ed using common and advanced technologies, and characterized for further bioactive properties, such as antibacterial activity, antioxidant activity, antidiabetic activity, anticancer activity, and so on. Such potential of betel vine made itself a green medicine in nature. It concludes that the betel vine keeps promising as a natural reservoir with regard to its nutritional, phar macological and economical aspects for the rapidly growing human population.