Baviskar H. P.*, Dhake G. T., Kasai M. A., Chaudhari N. B., Deshmukh T. A.
SES Arunamai College of Pharmacy, Mamurabad, Jalgaon (MS)
The Betle (Piper betle Linn.) is the leaf of a vine belonging to the Piperaceae family. The most likely place of origin of betle vine is Malaysia but it is also cultivated in India, Srilanka, Bangladesh, Burma and Nepal. Piper betel or Betel vine deep green heart shaped vary famous leaves belongs to the family Piperaceae called Paan leaves in India; rich in nutrients, minerals, vitamins, antioxidants, phytochemicals. Piper betel is mostly use to chew with sliced areca nut, slaked lime, coriander, aniseed, clove, cardamom, sweetener, coconut scrapings etc, but less used remedy. Focusing on traditional use and medicinal use of Piper betel we can cure many diseases and reduce the oral cancer which actually happens due to sliced areca nut, slaked lime not because of betel leaves. Leaves are rich in many nutrients like water, energy, protein, fats, fiber, calcium and iron etc. and the antioxidants present are flavonoids, tannins, saponins alkaloids, terpenoids etc. Piper betel helps in curing various diseases like diabetes, hypertension, brain toxin, halitosis, boils and abscesses, obesity, wound healing, voice problems, conjunctivitis, constipation, headache, hysteria, itches, mastitis, mastoiditis, leucorrhoea, otorrhoea, ringworm, swelling of gum, rheumatism, abrasion, cuts and injuries etc. So, we have to highlight these nutrients rich betel leaves and its benefits. In this review emphasis is lead upon research related to Therapeutic properties, Phytochemistry, and Pharmacological profile of Piper betle Linn.
Piper betel or Betel vine deep green heart shaped vary famous leaves belongs to the family of Piperaceae and has over 2000 species and indigenous to India. A wellprepared betel quid is still regarded as an excellent mouth freshener and mild vitalize, routinely served on the social, cultural and religious occasions like marriage, religious festivals, sraddha ceremony (religious function performed after cremation) etc.
The most likely place of origin of Piper betel vine is Malaysia but it is also cultivated in India, Srilanka, Bangladesh, Burma and Nepal. Piper betel leaves are popularly known as Paan leaves in India, which are consumed by about 15-20 million people in the country. It is cultivated following the traditional methods in India on about 55,000 hectare with an annual production worth about Rs 9000 million. On an average about 66% of such production is contributed by the state of West Bengal where it is cultivated on about 20,000 hectare encircling about 4-5 lakh Boroj employing about the same number of agricultural families1,2. Piper betel leaves are well-off in moisture, protein, fats, minerals, vitamins and in phytochemical and also antioxidants. It helps in curing and treatment of various diseases like halitosis, boils and abscesses, conjunctivitis, constipation, headache, hysteria, itches, mastitis, mastoiditis, leucorrhoea, otorrhoea, ringworm, swelling of gum, rheumatism, abrasion, cuts and injuries etc3. The vine is a dioeciously (male and female plants are different) shade loving perennial root climber. There are about 100 varieties of betel vine in the world, of which about 40 are found in India and 30 in West Bengal. The most possible place of origin of betel vine is Malaysia. In spite of its alikeness, the plant is much more popular in India than in any other country of the world since the distant past4. In these citations, significance of the leaves has been explained in relation to every sphere of human life including social, cultural, religious and even day-to-day life, which is very much relevant even these days5. This edible leaf has achieved an esteemed position in the human society right from the dawn of civilization. Particularly in the countries like Bangladesh, Burma, China, India, Indonesia, Malaysia, Nepal, Pakistan, Philippines, South Africa, Sri Lanka, Thailand. Leaves are traditionally used for chewing in their natural raw condition along with sliced areca nut, slaked lime, coriander, aniseed, clove, cardamom, sweetener, coconut scrapings, ashes of diamond, pearl, gold and silver, jelly, pepper mint, flavoring agent, fruit pulp. Based on the color, size, taste and aroma there are many varieties of betel leaf and some of the most popular Indian varieties are the Magadhi, Venmony, Mysore, Salem, Calcutta, Banarasi, Kauri, Ghanagete and Bagerhati4, 6. Piper betel vine is a tropical shadeloving perennial evergreen vine. It may climb as high as 10-15 ft. The Piper betel leaf prefers a warm and humid climate. Leaves are simple, alternate, ovate, cordate, acuminate or acute, entire and bright green. This plant has Male spikes which are dense and cylindrical while female spikes are pendulums. Roots arise from each node which aid in fixing the plant to the host tree. The color of pepper betel is yellowish green to dark green with glossy upper surface where as the odor is characteristic and pleasant. The betel leaves are aromatic with varied taste, ranging from sweet to pungent due to the presence of essential oils6, 7.
Piper betel is a Vedic plant and its Vedic name is Saptasira8 and in sankrit it known as Tambool, Nagvelleri, and Nagani9 were used as remedy against various diseases. In most of these texts were various medicinal properties has been highlighted. Reference to Tambool occurs right from Vatsyayana’s Kamasutra and Panchatantra down to Kalhan’s Rajatarngni (which may perhaps be the last of the recognise old Sanskrit writing of historical significance). Tambool has been referred to, thus roughly across a period of about 2000 year. In Ayurveda medicine system, the properties of betel leaf describe as given below10:
v Guna (Quality) :Laghu, Ruksha, Tikshan
v Rasa (Taste) :Tikta
v Vipak (Metabolism) : Katu
v Virya (Potency) : Ushan
v Prabhav (Impact) : Hridya
In Ayurveda betel leaf extract is frequently used as an adjuvant and mixed with different medicines possibly for better effects beside its independent use as medicine. In Susrta Samhita (Ch 28-46, 279-280) tambool leaves have been described as aromatic, sharp, hot, acrid and beneficial for voice, laxative, appetizer, beside this they pacify vata and aggravate pitta. In addition to these, the aphrodisiac effect of betel chewing has been indicated in ancient texts. Pan also believed to provide strength to heart and regulate blood. Its utility as anti-inflammatory and anti-microbial is emphasized at several place. In ayurveda it acts as vata and kapha suppressant. It also helps in expelling out the mucus from the respiratory tract because of its hot potency. According to Yunani system the leaf has a sharp taste and good smell improves taste and appetite, tonic to brain, heart and liver, lessens the thirst, clear the throat and purify the blood11.
Botanical name and Taxonomic Classification12,13:
v Kingdom: Plantae
v Division: Magnoliphyta
v Class: Magnolipsida
v Order: Piperales
v Family: Piperaceae
v Genus: Piper
v Species: betle
v Binomial name: Piper betle L.
v Sanskrit: Nagavallari, Nagini,Nagavallika,Tambool, Saptashira, Mukhbhushan, Varnalata
v Malaysia: Sirih, Sirih melayu, Sirih cina, Sirih hudang, Sirih carang, Sirih kerakap
v English: Betel, Betel pepper, Betel-vine
v Tamil: Vetrilai
v Telugu: Nagballi, Tamalpaku
v Hindi: Pan
v Gujurati: Nagarbael
v Marathi: Nagbael
v Bengali: Pan
v Arabic: Tambol, Tambool
v Semang: Serasa, Cabe
v Jakun: Kerekap, Kenayek
v Sakai: Jerak
v Javanese: Sirih, Suruh, Bodeh
v Thai: Pelu
Piper betel leaf has been described to have piperol-A, piperol-B, methyl piper betlol and they also have been isolated8. Piper betel leaves have an essential oil composing of terpinen-4-ol, safrole, allyl pyrocatechol monoacetate, eugenol, eugenyl acetate, hydroxyl chavicol, eugenol, piper betol and the betel oil contains cadinene carvacrol, allyl catechol, chavicol, pcymene, caryophyllene, chavibetol, cineole and estragol as the major components16,17.
Piper betel contains a wide variety of biologically active compounds whose concentration depends on the variety of the plant, season and climate. Chemical compositions of essential oil constitute safrole present in the leaf, stalk, stem, root and ß-phellandrene present in the fruit. The presence of hydroxychavicol acetate, allylpyrocatechol piperbetol, isoeugenol, anethole, stearic acid, methyl eugenol, carvacrol, polyphenol, alkaloids, saponin, tannin, steroids and other compounds are also found in Piper betel5. The aroma of betel leaf is due to the presence of essential oils, consisting of phenols and terpenes12. The active ingredient of piper betel oil which is obtained from the leaves is primary a class of allyl benzene compounds, chavibetol, chavicol, estragole, eugenol, methyl eugenol and hydroxycatechol18, 19.
Bio- Active Components:
Major constituents of Piper betel are chavibetol (53.1%) and chavibetol acetate (15.5%). Other constituents were allypyrocatechol diacetate (0.71%), campene (0.48%), chavibetol methyl ester (0.48%), eugenol (0.32%), α-pinene (0.21%), β-pinene (0.21%), a-limonene (0.14%), safrole (0.11%) and 1,8-cineole (0.04%). Hexane fraction of leaf stalks yielded four alipathic compounds in pure form pentadecyl 6-hydroxytridecanoate, pentatriacontanol, methyl hexacos-7-enoate and 6, 9-heptacosa diene. The principle chemical constituents of Piper betel were found to be polyphenols like eugenol, chavicol, charvacrol, chevibetol, catechol and allyl pyrocatechol and vitamin C, which were reported to exhibit strong antioxidant activity. Further these polyphenols exert their protective activities through their superior radical scavenging and immune modulating potentials20.
Piper betel possess various pharmacological properties include anticancer, antimutagenic, anti-amoebic, antigiardial, anti-inflammatory, mosquito larvicidal, antimicrobial, immunomodulatory, antiulcerogenic, radioprotective, antileishmanial, and antifungal activity17. In addition the leaf extract has also been reported to have antioxidant, antimicrobial, antifungal, anti-inflammatory and radio- protective properties. Piper betel leaf is also useful for the treatment of various diseases like bad breath, boils and abscesses, conjunctivitis, constipation, headache, hysteria, itches, mastitis, mastoiditis, leucorrhoea, otorrhoea, ringworm, swelling of gum, rheumatism, abrasion, cuts and injuries as folk medicine while the root is known for its female contraceptive effects21. Ethno Botanical Uses of Piper betel22
The leaf juice is given systemically to treat cough and indigestion in children and also as anti-malarial activity, antibacterial activity, antifungal study, insecticidal activities, antioxidant activity, anti-diabetic activity, gastro protective activity, antinociceptive activity, cytotoxic activity and anti-platelet.
Stems are supposed to be useful in treating indigestion, bronchitis, constipation, coughs and asthma.
Ø Whole Plant:
The plants of genus Piper are also used for many other purposes such as foods and spices, fish bait, fish poison, hallucinogens, insecticides, oils, ornaments, perfumes, antiwormal and anti-infectious agent because of its pungent taste. It helps in normalizing the digestive tract hence is very effective in maintaining the digestive system because of its light properties. Modern medicinal use23
Ø Betle leaves are beneficial in pulmonary infection in childhood and old age. The leaves, soaked in mustard oil and warmed, may be applied to the chest to relive cough and difficulty in breathing.
Ø Local application of the leaves is effective in treating sore throat. The crushed fruit or berry should be mixed with honey and taken to relieve irritating cough.
Ø Betle leaves are useful in treatment of nervous pain, nervous exhaustion and debility. The juice of few betle leaves, with a teaspoon of honey, will serve as a good tonic.
Ø Applied locally, betle leaves are beneficial in the treatment of inflammation such as arthritis and orchitis i.e. inflammation of the testes.
Ø Betle leaves have analgesic and cooling properties.
Ø It is also a valuable remedy for boils. A leaf is gently warmed till it gets soft, and is then coated with a layer of castor oil. The oiled leaf is spread over the inflammation.
Ø A hot poultice of the leaves or their juice mixed with some bland oil such as refined coconut oil can be applied to the loins with beneficial results in lumbago.
Ø The leaves can be used to heal wounds. The juice of the leaves should be extracted and applied on the wounds.
Ø The application of leaves smeared with oil is said to promote secretion of milk when applied to the breast during lactation.
Ø According to Unani system the leaf has a sharp taste and good smell which helps improve appetite. It also acts as a tonic to brain, heart and liver.
Ø It helps to promote healthy teeth and skin. Pharmacological Profile
The leaf has a significant antimicrobial activity against broad spectrum of micro-organisms.The betle shows the antimicrobial activity against Streptococcus pyrogenes, Staphylococcus aureus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa etc. Beside this the leaf extract also possess the bactericidal activity against the urinary tract pathogenic bacteria such as Enterocococcus faecalis, C.koseri, C.fruendi, Klebsiella pneumonia etc. The bioactive molecule thought to be responsible for anti-bacterial activity is sterol, which has been obtained in large quantities in betle leaf extracts. The mode of action may be due to surface interaction of sterol molecule present in the extracts with the bacterial cell wall and membrane leading to alteration in the primary structure of cell wall, ultimately lead to pore formation and degradation of the bacterial components. It is reported that sterol act through the disruption of the permeability barrier of microbial membrane structures. Gram-positive bacteria were more susceptible to the inhibitory effects of the plant extract because of single layer and lack the natural sieve effect against large molecules, whereas gram negative bacteria are multi layered and complex cell wall structure. The leaf has also poses the antifungal activity against many fungal infections. One of them is dermatophytosis. Dermatophytosis is a disease of the keratinized parts of the body (skin, hair, and nail) caused by athree genera (Trichophyton, Microsporum, and Epidermophyton) of highly specialized fungi called the Dermatophytes. The chloroform extract of Piper betle shows the much more efficiency than the methanol fraction against dermatophytes because of presence of non-polar components in the fraction.23
Protective and Healing Activity:
Most recently, a study was undertaken to evaluate the protective and healing effects of allylpyrocatechol against the indomethacin induced stomach ulceration in rat model. Results showed that allylpyrocatechol can protect indomethacin induced gastric ulceration due to its antioxidative and mucin protecting properties24.
Both the aqueous and ethanolic extracts of P. betle leaves possess marked hypoglycaemic activity when tested in fasted normoglycaemic rats. In glucose tolerance test, the extract showed antihyperglycaemic activity in the external glucose level. The ability of lowering blood glucose levels of streptozotocin (STZ) induced diabetic rat’s gives a suggestion that the extracts have insulinomimetic activity25.
The hot water extract significantly increased the mucus content adhering to the wall of the gastric mucosa. Mucus layer is considered to be important in mucosal defenses against endogenous aggressors, e.g., acids, and also as an agent in facilitate the repair process. It is generally believed that enhanced acid secretion is the most important factor for the induction of gastric lesions. The higher dose of hot water extract does not cause significant inhibition in acidity or pH of gastric fluid. Therefore, gastroprotective effect of Piper betle was not mediated via inhibition of acid secretion in the gastric mucosa but by increasing its mucus content. The gastroprotective activities of the higher dose of hot water extract significantly greater than Misoprostol. The extensive research has been proven that anti-oxidants might be effective mechanism not only in protecting against gastric mucosal injury, but also inhibiting progression of gastric ulceration. Ulceration progression is caused by free radical-induced chain process. Consequently, its arrest by radical scavengers helps in the faster healing. Allylpyrocatacol has shown a powerful anti-oxidant potential in various in-vitro models. Treatment with Allylpyrocatacol significantly accelerated the ulcer-healing process, which increases the mucus production usually assist the healing process by protecting the ulcer crater against irritant stomach secretion (HCl and Pepsin) thereby enhancing the rate of local healing process26.
Many of the disorders today are based on the imbalances of immunological processes. This necessitates the search for newer and safer immunomodulators. The methanolic extract has lymphocyte proliferation, interferon-C receptors and the production of nitric oxide were measured in vitro. Further, the extract at different dose levels was studied in vivo for the humoral and cellular immune responses on mice immunized with sheep red blood cells. The result showed that it significantly suppressed haemaglutinin stimulated peripheral blood lymphocyte proliferation in a dose-dependent manner. The decrease in antibody titre and increased suppression of inflammation suggests possible immunosuppressive effect of extract on cellular and humoral response in mice. From literature it conclude that betle leaf a novel candidate for immunosuppressive activity. The same could be further evaluated for its anticancer activity or as a potential candidate in the treatment of autoimmune disorders such as rheumatoid arthritis, systemic lupus erythomatous oremphysema27.
Platelet Inhibition Activity:
Hydroxychavicol (HC) was tested for its inhibition effect on platelate aggregation. The result showed hydroxychavicol to be a potent inhibitor for cyclooxygenase activity, reactive oxygen scavenger and inhibits platelet calcium signaling, thrombaxan B2 production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of artherosclerosis and other cardiovascular diseases through its anti-inflammatory and antipatelets effects, without effects on homeostatic function28.
As an Oral Care Agent:
Dental caries is a chronic endogenous infection caused by the normal oral commensally flora. The carious lesion is the result of demineralization of enamel and later of dentine by acids produced by plaque microorganisms as they metabolize dietary carbohydrates. The bacteria primarily responsible for dental decay in man are Streptococcus mutans. Streptococci belong to four main species groups: mutan, salivarius, anginosus and mitis. In addition to Streptococcis mutans, Lactobacillus acidophilus bacteria probably also pay a minor role in acid production in the plaque. The stickiness of the plaque is caused by dextran, which is produced by the fermentation of dietary sucrose by Streptococcus mutans. The plaque bacteria, particularly Streptococcus mutans, act on dietary fructose to produce lactic acid, which causes enamel decalcification (at below or above 5.5 pH). The plaque and dietary carbohydrates are in the initiation of enamel caries. Certain cariogenic and highly acidogenic strains of streptococci, especially S. mutans have the ability to metabolize dietary sucrose and synthesize glucan by cell-surface and extracellular glucosyl transferase. This enzyme is considered to be of special importance in the establishment of S. mutans in the dental plaque. The aqueous extract inhibit the different acid-producing oral pathogens which changes in the ultra-structure of the enamel and its properties like Streptococci, Lactobacilli, Staphylococci, Corynebacteria, Porphyromonas gingivalis and Treponemadenticola. So it is best natural substance and itsrating as second most popular daily consummation item in Asia, which contribute the best oral hygiene to oral cavity29.
Oxidative damage is an important effect of ionizing radiation on biological membranes. It is a chain reaction . Free radicals generated from the radiolytic decomposition of water can attack fatty acid chains of membrane lipid. A free radical that has sufficient energy to abstract an allylic hydrogen from the methylene carbon of polyunsaturated fatty acids can initiate the peroxidative process. Here the presence polyphenols compounds like chatecol, allylpyrocatecol etc. in betle leaf extract inhibited the radiation induced lipid peroxidation process effectively. This could be attributed to its ability to scavenge free radicals involved in initiation and propagation steps . The extracts reduced most of the Fe3+ ions and possess strong reductive ability . The extract also showed strong hydroxyl radical and superoxide anion radical scavenging property when compared with different standards such as ascorbic acid and BHT30,31,32,33.
A study to develop an orally effective male contraceptive agent was extensively carried out in male mice with various doses of the leaf stalks extract of Piper betle. The result shows no toxicity in all metabolically active tissue of mice and interestingly, the contraceptive efficacy emphasized reversible fertility after withdrawl of treatment34.
Hydroalcoholic extract of betle leaves exhibited improvement in the discrimination index, potentiating the haloperidol induced catalepsy, reduction in basal as well as amphetamine induced increased locomotors activity and delay in sodium nitrite induced respiratory arrest. These results from review suggest possible facilitation of cholinergic transmission and inhibition of dopaminergic as well as nor adrenergic transmission by the extract35, 36.
Pro-apoptotic Effect / Anti-Leishmaniasis:
In a comparative in vitro anti-leishmanial activity of methanolic extracts from two landraces of Piper betle. The PB-BM (P betle landrace Bangla Mahoba) selectively inhibited both stages of Leishmania parasites without macrophage cytotoxicity. The efficacy mediated through apoptosis is probably due to higher content of eugenol37.
Betle leaf rise in body temperature due to cholinergic responses. Aqueous and ethyl acetate extracts were evaluated for their cholinergic responses using isolated guinea-pig ileum. It was observed that the spasmogenic activity was more in water than ethyl acetate extract. In isolated rabbit jejunum K+-induced contraction was inhibited by both extract, suggesting blockade in calcium channel. Thus, leaves contain cholinomimetic and possible calcium channel antagonist constituents which may provide the basis for several activities shown by this plant38.\
The antihepatotoxic effect of betle leaf extract was evaluated on ethanol and carbon tetrachloride (CCl4) induced liver injury in a rat model. Fibrosis and hepatic damage, as revealed by histology and the activities of aspartate amino transferase (AST) and alanine amino transferase (ALT) were induced in rats by CCl4. The extract significantly inhibited the elevated activities of AST and ALT and also attenuated total glutathione S-transferase (GST), which led to a rise in antioxidant enzymes such as superoxide dismutase (SOD) and Catalase (CAT). The histological examination showed that the betle leaf extract protected liver from the damage induced by CCl4 by decreasing alpha smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2(MMP2) expression through the Ras/Erkpathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. These findings support a chemo preventive potential of betle leaf against liver fibrosis [56Anti-Photosensitizer Inhibitory property of the Piper betle phenolics against photosensitization-induced biological damages: PB phenolics, allylpyrocatechol (APC) may play a role in protecting biological systems against damage by eliminating O2 generated from certain endogenous photosensitizers39.
Mammalian system if exposed to radiation can cause damaging effects leading to cell death and an increased risk of degenerative diseases. Recently the radioprotective property of ethanolic extract of P. betle leaves was studied as alternative low cost preventive medicine to synthetic radio protectants which are reported to be toxic. The capacity of the extract in preventing g-ray induced lipid peroxidation and DNA damage in rat liver mitochondria were accessed and evaluated to establish the mechanism of its Radioprotective action. The study revealed significant immunomodulatory and superior radical scavenging activities which may be due to the presence of phenolic bioactives such as chavibetol and allyl pyrocatechol. It suggests that the herb has a great potential not only it is cheap but also easily accessible natural radioprotectant to the common people40.
Cytotoxicity / Anticancer Potential:
Study evaluated an aqueous extract of leaves to cytotoxicity studies on Hep-2 cell line. The mean CTC50 was 96.25 ug/ml suggesting potent cytotoxicity and probable anticancer property41, 42.
Study of rats on rats fed a dry powder of betle nuts, leaves and lime showed epidermal thickening in the upper digestive tracts in rats fed the betle nut mixed with lime and the betle leaves diet. A forestomach papilloma was seen in one rat on betle leaves diet. The epidermal changes were scarcely seen in rats on either betle nut or normal diet alone. Therapeutic Properties and Its Uses Nature has been a source of medicinal agents for thousands of years and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. Various medicinal plants have been used for years in daily life to treat disease all over the world. One of the medicinal plant i.e. Piper betle is a source of great economic value in the Indian subcontinent.
Ø Helps in Treatment of Disorders in physiological function, Skin diseases, and Eye diseases.
Ø It also has a diuretic property. Betle leaf juice given with milk or honey helps in easing urination.
Ø Betle leaf is considered aphrodisiac i.e. an agent which stimulates sexual desire.
Piper betel is very known to worldwide and consumed frequently as mouth freshener. These leaves are rich in nutrients, antioxidant, phytochemical and in many nutraceuticals properties but these are known to few people not to everyone. Removing the betel quid, areca nut, tobacco and other ingredients from the ‘Paan’ and having the leave with cardamom we can increase its beneficial part and reduce the side effects of it. Paper focuses on the beneficiary part of Piper betel plants. It is a traditionally used plant since antiquities as medicinally useful plant. So, we have to keep it using for curing diseases.
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Received on 03.04.2017 Modified on 18.04.2017
Accepted on 01.05.2017 ©AandV Publications All right reserved