Chemistry and medicinal properties of the Bakul (Mimusops elengi Linn): A review

Food Research International 44 (2011) 1823–1829

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Chemistry and medicinal properties of the Bakul (Mimusops elengi Linn): A review☆ Manjeshwar Shrinath Baliga a,⁎, Ramakrishna J. Pai b, Harshith P. Bhat d, Princy Louis Palatty c, Rekha Boloor b a

Department of Research and Development, Father Muller Medical College, Father Muller Road, Kankanady, Mangalore, Karnataka, 575003 India Department of Microbiology, Father Muller Medical College, Father Muller Road, Kankanady, Mangalore, Karnataka, 575003 India c Department of Pharmacology, Father Muller Medical College, Father Muller Road, Kankanady, Mangalore, Karnataka, 575003 India d Research Centre, Maharani Lakshmi Ammani Women's College, Malleswaram 18th Cross, Bangalore 560012, Karnataka, India b

a r t i c l e

i n f o

Article history: Received 5 October 2010 Accepted 28 January 2011 Keywords: Mimusops elengi Bakul Phytochemistry Pharmacology

a b s t r a c t India is one of the world's biodiversity hotspots and reports confirm that a great variety of fruiting trees are indigenous to this region of the world. Mimusops elengi Linn (family Sapotaceae) commonly known as Bakul is one such tree native to the Western Ghat region of the peninsular India. However, today this tree is also found growing in other parts of the tropical and subtropical regions of the world. The tree is of religious importance to the Hindus and finds mention in various mythological texts. The stem, barks, leaves and fruits are used in various Ayurvedic and folk medications to treat various ailments. In the prehistoric days the ripe fruits were an important source of diet but today no one knows of its dietary use as it is seldom used. Studies suggest the tree contains medicinally-important chemicals, particularly the triterpenes and alkaloids. Preclinical studies in the past five years have shown that the extracts prepared from Bakul possess antibacterial, antifungal, anticariogenic, free radical scavenging, antihyperglycemic, antineoplastic, gastroprotective, antinociceptive and diuretic effects, thus lending pharmacological support to the tree's ethnomedicinal uses in Ayurveda. In this review for the first time attempt is made at addressing the chemical constituents, medicinal uses and validated pharmacological observations of Bakul. © 2011 Elsevier Ltd. All rights reserved.

1. Introduction Mimusops elengi Linn (family Sapotaceae) colloquially known as the Spanish cherry, Medlar and Bullet wood in English is a tree aboriginal to the western peninsular region of South India (Mitra, 1981). In the ancient Indian language of Sanskrit the tree was known as Bakul and this term is adopted by many other Indian languages (enlisted in Table 1) (Mitra, 1981). The tree finds mention in the ancient Indian literatures like the Ramayana, Mahabharata, Abhijnana Shakuntala and Raghuvansha indicating its importance in the prehistoric days (Mitra, 1981). However, with time the trees had dispersed and are today found growing in other parts of India, the Andaman Islands, Burma, Pakistan, Thailand and parts of Northern Australia (Boonyuen, Wangkarn, Suntornwat, & Chaisuksant, 2009; Katedeshmukh, Shete, Otari, Bagade, & Pattewar, 2010). The tree is of great significance to the Hindus and the dried twigs of the tree are

Abbreviations: DPPH, 1,1-diphenyl-2-picrylhydrazyl; ABTS, 2,2′-azino-bis(3ethylbenzthiazoline-6-sulphonic acid); MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide; ROS, reactive oxygen species; IC50, inhibitory concentration 50; MIC, minimum inhibitory concentration; RNS, reactive nitrogen species. ☆ Dedication: The authors dedicate this paper to Dr. Roma Mitra of the Central Council for Research in Ayurveda and Siddha and the National Botanical Research Institute, Lucknow 226001 for her seminal work on Bakul. ⁎ Corresponding author. Tel.: + 91 824 2238331(office); fax: + 91 824 2437402, + 91 824 2436352. E-mail address: [email protected] (M.S. Baliga). 0963-9969/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.foodres.2011.01.063

used for various yajnas and religious rituals (Mitra, 1981). Reports suggest that in the ancient Indian civilization, the fruits were a staple diet of the sages, hermits and people (Mitra, 1981). However their usage has declined considerably and today very few people in India know of its dietary use. Currently, the fruits are a source of food to bats, parrots, crows, squirrels, monkeys, goats and cows. 2. Botanical description Bakul is a small to large evergreen tree reaching a height of about twenty meters and one meter in circumference (Fig. 1a). The bark is mostly fissured, thick, tough and heavy. It is brownish black or grayish black in color on the exterior and dark red inside. The trunk is straight with spreading branches and the canopy is very dense. The leaves are small, narrow, pointed, glossy, thick, dark green, oval in shape, and wavy at margin. They are about 5–16 cm in length and 3–7 cm in width (Fig. 1b). The heart wood is deep red in color, very hard and an excellent timber. The heartwood is a valuable wood and is in great demand for carving intricate designs. The ornate pillars, ceilings, windows and doors made from the Bakul wood are mostly found in the temples and palaces of South India (Jerline et al., 2009). The tree flowers once in a year and in India it is normally during the months of March to June. The flowers are star-shaped, small, yellowish white in color, hairy and occur in small clusters or in solitaire (Fig. 1b). The flowers are woven in to the form of a garland and offered in temples and shrines. They are powerfully scented and

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Table 1 Names of Mimusops elengi Linn in various languages (Jerline et al., 2009; Mitra, 1981). Language

Names

English Sanskrit

Spanish cherry, Medlar and Bullet wood Bakula, Bramarananda, Stri-mukhamadhu, Anankantha, Madhuparijara Maulseri, Molchari, Maulsiri, Bakula Bakul Bolsari, Barsoli Karak, Bakula, Pagade, Ranjal Omval Elengi, Ilanni, Ilenji Bokul lei Bakula, Barsoli, Avalli Alagu, Kesaram, Magilam, Mogadam, Nakum, Magizham Magizhamboo Kesari, Pogada, Vagula, magadam Molsari, Kirakuli Khaya Tanjong Kha-Yay Munnamal,Muhula, Muhuma Pikul

Hindi Bengali Gujarathi Kannada Konkani Malayalam Manipuri Marathi Tamil Telgu Urdu Burmese Malay Myanmar Sinhalese Thai

the fragrance is retained even when the flowers are completely dried. The process of fruiting takes about eight to ten weeks and the fruits are ovoid and 2 to 2.5 cm long. When raw the fruits are green in color and become yellow, golden orange to bright red–orange when fully ripe (Fig. 1c, d). The unripe fruits are astringent, while the ripen fruits are sweet and edible. The fruits contain one to two seeds and are ovoid, shiny, compressed and grayish brown in color (Jerline et al., 2009). 3. Proximate composition and phytochemistry Being a neglected fruit, the studies on the composition are very scanty. However recently, Nazarudeen (2010), studied the proximate composition of Bakul fruits growing in the dense forest regions of Western Ghats in Kerala, India and reported they contain moisture (79.27%), protein (1.29), fat (2.76%), reducing sugar (8.9%), nonreducing sugar (6.3%), total sugar (15.2%), fiber (1.13%), minerals (0.32%), vitamin C (3.27 mg/100 g), iron (0.59 mg/100 g), sodium (5.16 mg/ 100 g) and potassium (98.54 mg/100 g) (Nazarudeen, 2010). Chemical studies have shown that the bark contains taraxerol; taraxerone; urosolic acid (Fig. 2); betulinic acid (Fig. 2); α-spinosterol;

Fig. 1. Photograph of Bakul tree (1a), flowers (1b), raw and ripe fruits (1c) and a ripe fruit (1d). Courtesy of JM Garg (Wikipedia) and Tabish (flowers of India).

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Fig. 2. Important phytochemicals present in Bakul.

β-sitosterol (Fig. 2); lupeol (Fig. 2); the triterpenes, 3β, 19α, 23trihydroxy-urs-12-ene; 3β-(p-hydroxy-cis-cinnamoyloxy)urs-12-en28-oicac acid; 3β-(p-hydroxy-trans-cinnamoyloxy) urs-12-en-28-oic acid; fatty acid ester of α-spinasterol and farnan-2-one-3β-ol (mimusopfarnanol) (Hart, Johns, & Lamberton, 1968; Jahan, Ahmed, & Malik, 1995; Misra & Mitra, 1967, 1968; Nusrat, Wasim, & Abdul, 1995a; Nusrat, Wasim, & Abdul, 1995b). The flowers contain volatile oils (Mitra, 1981), while the leaves, heartwood and roots are known to have hentriacontane, carotene and lupeol (Misra & Mitra, 1967, 1968). The seeds are reported to contain the pentacyclic triterpenes, mimusopgenone and mimugenone (Sen, Sahu, & Mahato, 1995), triterpenoid saponins, such as mimusopsides A and B, mimusopin, mimusopsin, mimusin, Mi-saponin A and 16a-hydroxy Mi-saponin A, and gallic acid (Boonyuen et al., 2009; Lavaud, Massiot, Becchi, Misra, & Nigam, 1996; Sahu, 1996; Sahu, Koike, Jia, & Nikaido, 1995; Sahu, Koike, Jia, & Nikaido, 1997). The saponins like 3-O-(β-D-glucuronopyranosyl) 28-O-(α-L-rhamnopyranosyl (1 → 3) β -D-xylopyranosyl (1 → 4) [α-L-rhamnopyranosyl(1 → 3)] α-L-rhamnopyranosyl(1 → 2) α-L-arabinopyranosyl) protobassic acid, 3-O-(β-D-glucuronopyranosly) 28-O-(α-L-rhamnopyranosyl(1 → 3) β-D-xylopyranosyl (1 → 4) α-L-rhamnopyranosyl(1 → 2) α-L-arabinopyranosyl) 16-αhydroxyprotobassic acid and 3-O-(β-D-glucopyranosyl(1 → 3) β-Dglucopyranosyl) 28-O-( α-L-rhamnopyranosyl(1 → 3) β-D-xylopyranosyl(1 → 4) α-L-rhamnopyranosyl(1 → 2) α-L-arabinopyranosyl) protobassic acid have also been isolated from the seed kernel (Lavaud et al., 1996).

4. Uses in traditional medicine In the traditional Indian system of medicine, the Ayurveda Bakul is an important tree and is mentioned in Charaka Samhita, Sushruta Samhita, Astanga Hrudaya, Bhavaprakasa, Dhanvantari and Saligrama (Mitra, 1981; Nadkarni, 1976). In Ayurveda, the bark, flowers, fruit and seeds are of great value for treating various ailments. According to Sushruta, the revered priest of Ayurveda, Bakul possesses astringent cooling, anthelmintic, tonic, and febrifuge properties and is useful in alleviating kapha and pitta doshas (Mitra, 1981; Nadkarni, 1976). The bark and flowers are used to prepare classical Ayurvedic formulations like Bakuladya taila, Bakula puspa churna and Bakula tvak kvatha (Mitra, 1981; Nadkarni, 1976).

In prehistoric days the powder of the bark skin and the tender stems were used like tooth brush for cleansing the teeth. In Ayurveda, the decoction prepared from Bakul is recommended for treating various dental ailments and to keep the gums healthy. Rinsing mouth with bark decoction is believed to strengthen the gums, reduce inflammation, prevent bleeding of gums, and to stop bad breath caused by pyorrhea and dental caries (Mitra, 1981). Additionally, the bark or leaf decoction is also supposed to be useful in cleaning dermal wounds, for ulitis and ulemorrhagia. It is also reported to possess anti-ulcer effects and to increase the fertility in women (Anonymous, 1969; 2000). The decoction is regarded to be useful as a tonic and febrifuge. The tender stems are also supposed to be of use in the treatment of urethrorrhea, cystorrhea, diarrhea and dysentery. The bark of M. elengi possesses cardiotonic, alexipharmic, stomachic, antihelmentic and astringent activity (Shah, Gandhi, Shah, Goswami, & Santani, 2003). The snuff made from the dried flowers is supposed to be useful in the treatment of Ahwa a disease with strong fever, headache and pain in the neck, shoulders and other parts of the body (Mitra, 1981). The snuff is also believed to be a neurotonic and to relieve headache and cephalalgia. The lotion prepared from the flowers is believed to be effective in healing for wounds and ulcers (Mitra, 1981; Nadkarni, 1976). The decoction of the flowers is believed to be useful against heart diseases, to act as antiduretic in polyuria, as an antitoxin, to treat leucorrhoea and menorrhagia (Mitra, 1981; Nadkarni, 1976). The fruits are believed to be effective in preventing chronic dysentery and constipations. The unripe fruit is used as a masticatory and is supposed to be helpful in fixing loose teeth. It is supposed to prevent premature ejaculations, to possess antidiuretic effects and is also useful as an anti-toxin. The ripe fruit is supposed to be a general tonic and to decrease the vitiated pitta dosha (Mitra, 1981; Nadkarni, 1976). The aqueous concoctions of the fruits are believed to promote delivery during childbirth. Ripened fruits are supposed to ease urination, alleviate burning micturition and help in the removal of urinary calculi (Mitra, 1981; Nadkarni, 1976).

5. Validated studies Being an indigenous tree and localized to selected geographical pockets of India, the scientific studies, especially on the pharmacological properties of Bakul have been minimal. In the following sections the

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Table 2 Effect of Bakul in exerting the various pharmacological properties in experimental systems of study. Pharmacological properties

Observations and references

Antioxidant effects

1. The methanolic extract of the Bakul leaves (95%) is reported to be effective in DPPH, total antioxidant and reducing power assays in vitro (Saha et al., 2008). 2. The extract prepared from immature green, mature green and orange ripe fruits and the various fraction free phenolic acids, soluble phenolic esters and insoluble phenolic acid esters possess free radical scavenging activities in both DPPH and ABTS assays (Boonyuen et al., 2009). 3. The methanolic extract of the stem bark is reported to possess ferric ion reducing antioxidant power, DPPH and hydroxyl radical scavenging activity in vitro (Ganu et al., 2010). 1. The aqueous and ethanolic extracts of the Bakul leaves are shown to possess antibacterial action (Nair & Chanda, 2007). 2. The petroleum ether, ethyl acetate and methanolic extracts of the bark, fruits and leaves also possess antibacterial effects (Ali et al., 2008). 3. Extracts from bark, fruit and seed are also shown to be effective (Shahwar and Raza, 2009). 4. Pentahydroxy flavones 2,3-dihyro-3,3′4′5,7-pentahydroxyflavone and 3,3′,4′,5,7-pentahydroxyflavone isolated from the ethyl acetate extract of the seed are shown to be effective on Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633 and Salmonella typhi ATCC 6539 (Hazra et al., 2007). 1. The petroleum ether, acetone, methanol and aqueous extracts of the plant are highly effective on various cariogenic bacteria (Ajaybhan et al., 2010).

Antibacterial

Anti-cariogenic effects Antifungal activity Gastroprotective effects Hypotensive effects Antidiabetic activities Diuretic activity Antineoplastic effects

1. The petroleum ether, ethyl acetate and methanolic extracts of the bark, fruits and leaves are shown to possess antifungal activity (Ali et al., 2008). 1. Bakul is shown to be effective in reducing ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcerations in rats (Shah et al., 2003). 1. The methanolic extract of Bakul is shown to possess hypotensive activity in anesthetized rats (Dar et al., 1999). 1. The aqueous extract of the bark is shown to possess hyperglycemic effects in alloxan induced diabetic rats. The extract decreased blood glucose and glycosylated hemoglobin, increased serum insulin levels and rectified some glucogenic enzymes (Jerline et al., 2009). 2. The methanolic extract of the stem bark also possesses anti-hyperglycemic effect (Ganu et al., 2010). 1. The ethylacetate, ethanolic, methanolic and aqueous extracts of the bark possess diuretic effects. The aqueous extract was the best (Katedeshmukh et al., 2010). 1. The ethanolic extract (95%) of Bakul is shown to possess cytotoxic effects on cultured cholangiocarcinoma cells (CL-6), human laryngeal carcinoma cells (Hep-2) and human hepatocarcinoma cells (HepG2) in vitro (Mahavorasirikul et al., 2010).

scientifically validated pharmacological properties are addressed (Table 2). 5.1. Antibacterial activities Since its discovery and clinical development, antibiotics have been the main stay in the treatment of bacterial infections for nearly seven decades (Arias & Chopra Murray, 2009). However the imperfect adherence to the prescribed schedule by the patients and indiscriminate use of antibiotics by the physicians have contributed to the development of drug resistant bacteria which fail to respond to the conventional treatment and resulted in prolonged illness and enhanced the risk of death (Arias & Chopra Murray, 2009; Raghunath, 2010). Therefore efforts are on at a global level to discover and develop novel agents, and natural products and phytochemical are also investigated for their antibacterial effects. Nair and Chanda (2007) studied the antibacterial effects of the aqueous and ethanolic extracts of the Bakul leaves on the medically important bacterial strains such as the Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Bacillus cereus, Alcaligenes faecalis and Salmonella typhimurium. They observed that both the extracts were ineffective on P. aeruginosa and S. typhimurium, while they were effective in all other strains of organisms. The ethanolic extract was more effective on B. cereus and P. mirabilis, while the aqueous extract was effective on A. faecalis and S. aureus (Nair & Chanda, 2007). Ali, Mozid, Yeasmin, Khan, and Sayeed (2008) investigated the antibacterial effects of the petroleum ether, ethyl acetate and methanolic extracts of the bark, fruits and leaves of Bakul (300 mg/ disk) with Kanamycin (30 mg/ disk) as the positive control on both gram positive (S. aureus, Streptococcus beta haemolyticus and Bacillus subtilis) and gram negative organisms (Klebsiella species, Shigella shiga, Shigella boydii and Shigella dysenteriae) by the disk diffusion method in vitro. The bark and fruit extracts were observed to be more effective on the gram positive organisms, especially on S. aureus and B. subtilis. The antibacterial activity of the leaf extracts was almost similar in the two types of organisms. However none of the extracts were as effective as the standard Kanamycin (Ali et al., 2008). Shahwar and Raza (n.d.) studied the antibacterial effects of various extracts from bark, fruit and seed against gram positive and gram negative strains (Nocardia asteroids NRRL 174, Micrococcus luteus ATCC 10240,

Bacillus subtilis PCSIRB 248, Bacillus licheniformis NCL 2024, Proteus mirabilis ATCC 29425 and Salmonella typhimurium ATCC 14028) by the MIC. The stem bark extracts showed antibacterial activity against all the organisms, while the extracts of fruit and seed were inactive. The extracts were more effective on the gram-positive bacteria. The ethyl acetate extract showed potent effects (84.5%) against B. subtilis, while the aqueous methanol extract was effective against N. asteroids (74.9%) and was equal to that of streptomycin and ampicillin used as standards (Shahwar & Raza, n.d.). The pentahydroxy flavones 2,3-dihyro-3,3′4′5,7-pentahydroxyflavone and 3,3′,4′,5,7-pentahydroxyflavone isolated from the ethyl acetate extract of the seed possess antibacterial effects on Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633 and Salmonella typhi ATCC 6539 (Hazra, Roy, Sen, & Laskar, 2007). 5.2. Anti-cariogenic effects Dental caries, which affects the tooth, can cause decalcification of the enamel or the dentine. It is caused by a range of oral pathogenic microorganisms. The cariogenic Streptococci are critical to the development of pathogenic plaque, while a certain strains of Streptococcus, Actinomyces and Lactobacillus are involved in root caries and periodontal diseases (Ajaybhan, Navneet, & Chauhan, 2010; Slots & Rams, 1992). In the Ayurvedic system of medicine, use of Bakul has been advocated for dental care and scientific studies have validated these observations. Preclinical studies by Ajaybhan et al. (2010) have shown that the petroleum ether, acetone, methanol and aqueous extracts of the tree were effective on the S. aureus, Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, Lactobacillus acidophilus and Candida albicans. Among the four extracts the methanolic extract was observed to be the most potent followed by aqueous, acetone and petroleum ether extracts (Ajaybhan et al., 2010). 5.3. Antifungal effects Globally, opportunistic fungal infections are on a rise and a major cause of morbidity and mortality especially, in the immunocompromised patients (Fostel & Lartey, 2000). In clinical settings, fluconazole and itraconazole are the most commonly used antifungal agents. However their systemic consumption is known to produce toxic effects. The

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development of resistance by certain fungal strains to the existing antifungal drugs has further complicated the treatment option and this has emphasized the need for developing more effective and nontoxic antifungal agents (Fostel & Lartey, 2000). Ali et al. (2008) investigated the antifungal effects of the petroleum ether, ethyl acetate and methanolic extracts of the bark, fruits and leaves of Bakul (300 mg/disk) with fluconazole (50 mg/disk) as the positive control on Penicillium sp., Aspergillus niger, Trichoderma viride, Aspergillus flavus, C. albicans and Helminthosporium sativum. Among the three parts studied, at a single dose of 300 mg/disk, the bark and the leaves were observed to be more effective than the fruits. However when compared with fluconazole (50 mg/disk), none of the extracts were effective, suggesting their limited usefulness. 5.4. Antioxidant effects Excess production of free radicals (ROS and RNS) causes damage to the DNA, lipids, proteins, and other biomolecules. Accordingly, inhibition of free radical generation free radical is important and studies have shown that many plants, fruits and dietary compounds are effective (Alia et al., 2008; Rufino et al., in press; Sánchez-Moreno, Larrauri, & Saura-Calixto, 1999). With regard to Bakul, Saha et al. (2008) evaluated the free radical scavenging effects of the methanolic extract (95%) of the Bakul leaves in DPPH radical scavenging, total antioxidant capacity and reducing power assays in vitro (Saha et al., 2008). In the DPPH radical scavenging assay a concentration dependent activity was seen (1 μg to 500 μg). The IC50 value of the extract was calculated and observed to be 43.26 μg/ml, and the free radical scavenging effect was better than that of ascorbic acid (IC50 55.89 μg/ml), used as positive control. Similar results were also observed in the total antioxidant capacity at all the concentrations studied (100 to 800 μg/ml) and optimal effect was observed at 800 μg/ml. In the assay aimed at understanding the reducing power of the extract (100 to 1000 μg/ml), a concentration dependent effect was observed and the optimal effect was seen at 1000 μg/ml (Saha et al., 2008). Recently, Boonyuen et al. (2009) investigated the antioxidant effects of the crude extract [prepared using 70% methanol in water and 70% acetone in water (1:1)], free phenolic acids (F1), soluble phenolic esters (F2) and insoluble phenolic acid esters (F3) extracted from immature green, mature green and orange ripe fruits of Bakul by the DPPH and ABTS scavenging assays in vitro and expressed as gallic acid equivalents. The authors observed that the antioxidant effects of the crude extracts were as follows: immatureN matureN ripe (Boonyuen et al., 2009). The antioxidant capacity values in the ABTS and DPPH assays for these phenolic fraction of the crude extract in the immature and mature stages were F2N F3N F1. However with the ripe fruits, in the ABTS assay the results indicate F2 N F3N F1, while in the DPPH assay it was F3 N F2 ≈ F1. Phytochemical studies also showed that gallic acid was present in the fruits and that the highest amounts of phenolics in the form of soluble phenolic acid esters were in the F2 fraction of the mature stage. Together these observations clearly indicate that the increased concentration of gallic acid in the F2 fraction were responsible for the better free radical scavenging activities of the F2 fraction in both DPPH and ABTS assays (Boonyuen et al., 2009). Studies have also shown that the methanolic extract (10 to 100 μg/ml) of the stem bark also possesses ferric ion reducing antioxidant power, DPPH and hydroxyl radical scavenging activities in vitro. However the effects of the extract in all the three assays were inferior to that of the ascorbic acid used as the positive control. Together these results clearly suggest that both leaf and fruit possess antioxidant effects and that the ripe fruits could also be a potential source of natural antioxidant (Ganu, Jadhav, & Deshpande, 2010). 5.5. Gastroprotective effects Peptic ulcer, which results from imbalance between aggressive and protective factors, is a serious gastrointestinal disorder. Clinically,

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the use of proton pump inhibitors and H2 receptor antagonists is recommended but incidence of relapses, side effects and drug interactions are common (Shah et al., 2003). This has necessitated the need for developing new antiulcer drugs that are effective and nontoxic at their optimal therapeutic concentrations when used for extended periods of time. Shah et al. (2003) investigated the gastroprotective effects of 50% alcoholic extract of Bakul (50, 100, 300 and 500 mg/kg) against the ethanol-induced, pylorus-ligated and water-immersion plus stressinduced gastric ulcer models in rats with ranitidine HCl (80 mg/kg) and pantoprazole (20 mg/kg) as positive control drugs. Oral administration of the extract before administering the ulcerogens significantly reduced the severity of ulcerations. Similar effects were also observed when the ethyl acetate, n-butanol, methanol and aqueous fractions of the alcoholic extract were administered at a single concentration of 100 mg/kg. Of these fractions, the best gastroprotective activity was observed with the ethyl acetate fraction and a concentration dependent (50, 100, 300 and 500 mg/kg) gastroprotective effect against the ethanol-induced gastric damage was observed (Shah et al., 2003). When compared with the control group, in the 19 h pylorusligation model the ethyl acetate extract at 50 and 100 mg/kg concentration was also effective in reducing total acidity, volume of gastric acid secretion, total acid output and pepsin activity and this was partly due to the increased levels of mucosal glycoproteins and mucin activity. The ethyl acetate extract also showed a dose dependent protection against water-immersion plus stress-induced lesions. The levels of ulcer index, total lesion area and score for intensity of intraluminal bleeding were decreased when compared with the control group. Together these observations clearly suggest that the 50% ethanolic extract of Bakul and its ethyl acetate fraction were effective in reducing gastric ulcerations induced by various ulcerogens. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms (Shah et al., 2003). 5.6. Antidiabetic effects Diabetes mellitus a disease as old as mankind is today the world's leading endocrine related ailment. It affects nearly 5% of the global population and predictions are that the number will increase from the present estimates of 150 million to 230 million in 2025 presenting a major challenge to the global health care sector (Ganu et al., 2010). Jerline et al. (2009) investigated the antihyperglycemic effects of the aqueous bark extract of Bakul (250 and 500 mg/kg for 45 consecutive days) with glibenclamide (1 mg/kg b. wt.) as the positive control in alloxan induced preclinical diabetic model in rats. A concentration dependent effect was observed and the antihyperglycemic effects observed in the cohorts administered with Bakul (500 mg/kg b. wt.) was comparable to that of the cohorts receiving glibenclamide. The study clearly showed that the oral administration of the extract caused a significant decrease in the levels of blood glucose and glycosylated hemoglobin, and concomitantly increased the serum insulin levels. When compared with the diabetic controls, the levels of glycogen, glucokinase, and glucose-6-phosphate dehydrogenase were increased in the liver of the extract administered cohorts, while that of glucose-6-phosphatase were decreased suggesting rectification of the altered metabolism (Jerline et al., 2009). Recently, Ganu et al. (2010) investigated the antidiabetic effects of the methanolic extract of the stem bark of Bakul in allaxon-induced model in mice. The methanolic extract was administered at 100, 200 and 400 mg/kg b. wt. was effective in reducing hyperglycemia in rats. In a single day anti-hyperglycemic study, administration of the extract significantly reduced the serum glucose level at two hours post administration. However the highest effect was seen at six hours and persisted up to twenty four hours post treatment. The effect was

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comparable to that of glyburide (10 mg/kg, p.o.) used as positive control. In the oral glucose tolerance test with the diabetic mice, administration of the extracts two hours before administering glucose (2.5 g/kg, p.o.) caused a dose dependent anti-hyperglycemic effect at all the time points studied. Similar observations were observed in the oral glucose tolerance test in nondiabetic mice. The extract was devoid of any systemic or neurological effects as no death or an alteration in the behavior was observed. The LD50 was greater than 5000 mg/kg when administered orally suggesting the extract to be safe (Ganu et al., 2010). 5.7. Diuretic effects Diuretics, drugs which can increase the volume of urine are extremely beneficial in the treatment of diseases related with the retention of fluids, like in cardiac failure, acute edema of the lung, nephritic edema syndrome, arterial hypertension, etc. (Dussol, Moussi-Frances, & Morange, 2005). With regard to Bakul, Katedeshmukh et al. (2010) evaluated the antidiuretic effects of the ethylacetate, ethanolic, methanolic and aqueous extracts of the defatted bark in Wistar rats. The authors administered either saline (25 ml/kg b.w.) or 250 mg/kg b. wt. of the various extracts orally, or furosemide (20 mg/kg) i.p. or mannitol (100 mg/kg) intravenously. Following this the animals were placed in metabolic cages to evaluate the volume of urine at different time points (1, 2, 4, 6 and 24 h) of post administration. When compared to the saline treated cohorts, the administration of 250 mg/kg b. wt. of the various extracts increased the volume of urine and excretion of Na+ at all the estimated time points. The efficacy was as follows: aqueous extract N ethanolicN ethylacetate extracts. The aqueous extract was observed to be a better diuretic than mannitol but less than furosemide. The extract did not produce any mortality or adverse reaction after the administration of a single high limit dose of 2 g/ kg b. wt., suggesting it to be nontoxic and safe. 5.8. Hypotensive effect Despite advances in modern medicine, arterial hypertension remains a major health problem and often predisposes individuals to cardiovascular disease and mortality. Recent reports indicate that it afflicts N72 million people in the United States and N1 billion people worldwide and is mostly an incurable disease (Rosamond, Flegal, & Friday, 2007). In most instances the patients fail to understand the need for prolonged treatment and to complicate the prophylaxis, the existing, hypotensive drugs are expensive and are often badly tolerated, necessitating the need for drugs that are effective and affordable (Rosamond et al., 2007). Preclinical studies have shown that the methanolic extract of Bakul caused hypotensive activity in anesthetized rats. The intravenous administration of the extract at a dose range of 2–16 mg/kg, produced about a 7–38% decrease in mean arterial blood pressure and the effect was concentration dependent. The effect was observed to be independent of adrenergic, muscarinic and histaminergic receptors and the hypotension was unchanged after autonomic ganglion or angiotensin-convertingenzyme blockade. However, administration of calcium channel blockers [nifedipine (0.9 mg/kg) and verapamil (3.9 mg/kg)], caused a decrease of 81 and 64% in extract-induced hypotension, thereby suggesting that the extract possesses calcium-blocking activity and resulted in the observed effects (Dar, Behbahanian, Malik, & Jahan, 1999).

for the conventional chemotherapeutic agents which are effective in controlling the cancer at nontoxic doses and inexpensive. Mahavorasirikul, Viyanant, Chaijaroenkul, Itharat, and Na-Bangchang (2010) evaluated the antineoplastic effects of the ethanolic extract (95%) of Bakul flowers on the cholangiocarcinoma cell line CL6, human laryngeal carcinoma cell line Hep-2, human hepatocarcinoma cell line HepG2 and normal human epithelial cell (HRE) in vitro with 5-fluorouracil as the positive control and cytotoxicity assay as the end point. Cultured cells which were in log phase were treated with various concentrations of the extract (1.95 to 250 μg/ml) or 5fluorouracil (78.13 to 10,000 μM) for 24 h and the cytotoxic effects were evaluated by the MTT assay. The study showed that a concentration dependent cytotoxic effect was observed and the IC50 were 48.84, 109.99 and 54.44 μg/ml, for CL-6, Hep-2 and HepG2 cells, respectively. 6. In food protection Fungi like Aspergillus sp., Fusarium sp. and Penicillium sp. infest grains, fruits and vegetables, affecting their nutritive value, producing the dangerous mycotoxins and render them unfit for human consumption (Galvano, Piva, Ritienei, & Galvano, 2001). In a conventional setup, synthetic antifungal agents are used to control fungal infestation. However repeated use of synthetic fungicide is not recommended as it causes detrimental health effects to the people employed and may also lead towards soil and water pollution. Therefore in recent times emphasis is on the use of eco-friendly and nontoxic metabolites for the management of fungi and use of plant metabolites is an attractive option (Satish, Raghavendra, Mohana, & Raveesha, 2010). Satish et al. (2010), investigated the antifungal effects of the aqueous, petroleum ether, benzene, chloroform, methanolic and ethanolic extracts of Bakul leaves in vitro on a range of phytopathogenic fungi belonging to Alternaria alternata, Drechslera, Fusarium, Aspergillus and Penicillium, that frequently infest sorghum [Sorghum bicolor (L.) Moench], maize (Zea mays L.) and paddy (Oryza sativa L.) seeds. It was observed that the aqueous, methanolic and ethanolic extracts possess high antifungal activity against all the tested fungi than the other extracts at the tested concentrations (10, 20, 30, 40 and 50%). The methanolic extract was further fractionated and subjected to activity guided assay on these fungi. The results indicated that when compared to synthetic fungicides like Dithane M-45, Blitox and Captan 45, the antifungal activity of alkaloid fraction is highly significant and could be of possible use (Satish et al., 2010). 7. Conclusions Studies carried out in the recent past indicate that Bakul possesses diverse health benefits like antibacterial, antifungal, anticariogenic, free radical scavenging, antihyperglycemic, antineoplastic, gastroprotective, antinociceptive and diuretic effects properties. Future studies should be with isolated phytochemicals as these will improve our understanding the mechanism of action responsible for the various beneficial effects. The outcome of these investigations will determine the possible development of drugs from it. When compared to the prehistoric days, the consumption of Bakul fruits is less and most of the fruits drop and go wasted or are eaten by birds and animals. The fruits are good source of nutrients and are low in calories. Their regular consumption could benefit people with obesity and metabolic syndromes.

5.9. Anticancer effects Acknowledgments Chemotherapy, which is one of the important arms of cancer treatment, is accompanied with severe side effects which at times negate the therapeutic benefits (Dorr & Fritz, 1980). Further many of the clinically used drugs are very expensive and unaffordable for people in the developing countries. Therefore efforts are on to discover substitutes

The authors are grateful to Rev. Fr. Patrick Rodrigus (Director), Rev. Fr. Denis D'Sa (Administrator), Dr. Sanjeev Rai (Chief of Medical Services) and Dr. Jayaprakash Alva, (Dean) of Father Muller Medical College for their unstinted support. The authors are grateful to JM Garg

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