Aegle marmelos: A phytochemical and phytopharmacological review

Pharma Admission

Pharma courses

pharma admission

pharma courses

 

Anti proliferative and Radio protective activity
It had been revealed that various extracts of stem bark of Aegle marmelos Corr. were able to inhibit the in-vitro proliferation of human tumour cell lines, including the leukaemic K562, T-lymphoid Jurkat, B-lymphoid Raji, erythroleukemic HEL, melanoma Colo38, and breast cancer MCF7 and MDAMB-231 cell lines. Molecules present within the A. marmelos extracts were identified by gas-chromatography/mass-spectrometry analysis; three derivatives (butyl p-tolyl sulphide, 6- methyl-4-chromanone and butylated hydroxyanisole) were found to exhibit strong activity in inhibiting in vitro cell growth of human K562 cells. The anti proliferative activity of these compounds was comparable to that of known anti tumour agents, including Cisplatin, Chromomycin, Cytosine arabinoside and 5-fluorouracil. In addition, the anti proliferative activity of butyl-p-tolyl sulphide, 6-methyl-4-chromanone and 5-methoxypsolaren was associated to activation of the differentiation pattern of K562 cells [30].

The anticancer effect of hydro alcoholic extract of Aegle marmelos (AME) was studied in the Ehrlich Ascites Carcinoma bearing Swiss albino mice. The spatial effect of various AME administration schedules showed that six-day administration increased the survival of tumour bearing mice. The best anti neoplastic action of AME was observed on its intraperitoneal route. Administration of AME once daily for six consecutive days to the tumour bearing mice caused a dose dependent remission of the tumour at 400 mg/kg body weight, where the greatest anti tumour effect was observed and the higher doses showed toxic manifestations. A 24 day lengthening in life span was observed in EAC animals treated with 400 mg/kg AME. This dose of 400 mg/kg was considered as the best dose, where the animals survived upto 43 day post-tumour-cell inoculation as against no survivors in the saline treated control group. The AME treatment resulted in a dose dependent elevation in the median survival time (MST) and average survival time (AST) up to 400 mg/kg AME and declined thereafter. The effective dose of 400 mg of AME was 1/6 of the LD50 dose, which increased the MST and AST up to 29 and 27 day, respectively [78].

The radio protective effect of hydro alcoholic extract of leaves of Aeglemarmelos (AME) was evaluated in cultured human peripheral bloodlymphocytes (HPBLs) by the micronucleus assay. The optimum protectivedose of the extract was selected by treating HPBLs with1.25,2.5, 5, 6.25, 10, 20, 40, 60, 80 and 100 µg/ml AME beforeexposure to 3 Gy -radiation and then evaluating the micronucleusfrequency in cytokinesis blocked HPBLs. Treatment of HPBLs withdifferent doses of AME reduced the frequency of radiation-inducedmicronuclei significantly, with the greatest reduction in micronucleusinduction being observed for 5 µg/ml AME. The irradiation of HPBLs withdifferent doses of γ -radiation caused a dose-dependent increasein the frequency of lymphocytes bearing one, two and multiplemicronuclei, while treatment of HPBLs with 5µg/ml AMEsignificantly reduced the frequency of lymphocytes bearing one,two and multiple micronuclei when compared with the irradiatedcontrol. The dose–response relationship for both groupswas found out to be linear. AME was foundto inhibit free radicals in a dose-dependent manner up to adose of 200µg/ml [79].

The radio protective effect of a hydro alcoholic extracted materialfrom the fruit of Aegle marmelos (AME) was studied in mice exposedto different doses of γ-radiation. The optimum dose for radio protectionwas determined by administering 0, 5, 10, 20, 40, or 80 mg/kgbody weight of AME intraperitoneally once daily, consecutivelyfor 5 days before exposure to 10 Gy of γ-radiation. A total of20 mg/kg of AME for 5 consecutive days before irradiationwasfound to afford maximum protection as evidenced by the highestnumber of survivors after 30 days post irradiation. Animals fromall groups were monitored for 30 days post irradiation for developmentof symptoms of radiation sickness and mortality. Treatment ofmice with AME before exposure to different doses of γ radiation reduced the severity of symptoms of radiation sickness and mortalitywith all exposure doses. Treatment of animals with AME before irradiation causeda significant decrease in the lipid peroxidation accompaniedby a significant elevation in the GSH concentration in liver,kidney, stomach, and intestine of micedeterminedafter 31 dayspost irradiation [80].

Anti thalessemic activity
Extract of A. marmelos has been reported to stimulate the production of fetal haemoglobin in adults and can be used as a possible remedy for β-thalassemia [81].

Antimicroflarial activity
A study has explored that methanolic extracts of leaves of A. marmelos Corr. has antifilarial effect against Brugia malayi microfilariae as it was observed that leaves extract at 100 ng/ml concentration showed complete loss of motility of microfilariae after 48 hr of incubation. Coumarin in the leaves of A. marmelos Corr. are known to be responsible for the activity [82].

Larvicidal activity
Aegle marmelos has been reported to possess moderate larvicidal activity against early fourth-instar larvae of Culex quinquefasciatus [83].

Wound healing activity
The root bark extract of Aegle marmelos was found to promote wound healing in both normal and immunocompromised (steroid treated) rats in a space wound model. The plant increased not only lysyl oxidase activity but also, protein and nucleic acid content in the granuloma tissue indicating it probably exert their action at the cellular (nuclear) level. It also increased the tensile strength of the granuloma tissue due to the result of the increase in the glycosaminoglycan content. Thus A. marmelos root bark not only hastened normal healing, but also reversed steroid depressed healing [84].

Effect on enzyme kinetics
Leaf extract of Aegle marmelos was found to significantly reverse the raised Km values, but not Vmax values of the enzyme malate dehydrogenase, an important enzyme in glucose metabolism [85].

Abortifacient activity
Aqueous extract of A. Marmelos leaves has been reported to exhibit significant abortifacient activity in rats [86].

Anti amnesic activity
A study was undertaken in which Chywanprash (containing A. marmelos as one of the ingredient) at the dose of 1 and 2% w/w of diet administered daily for 15 successive days in mice with memory deficits. The administration of Chywanprash for 15 consecutive days significantly protected the animals from developing memory impairment. Furthermore, there was a significant decrease in brain TBARS and increase in GSH levels after administration of Chywanprash (2% w/w), thereby indicating decreased free radical generation and increased scavenging of free radical, respectively [87].

Toxicity studies
The acute toxicity study of AME showed that the drug is non-toxic up to a dose of 1750 mg/kg body weight. The LD10 and LD50 were found to be 2000 and 2250 mg/kg respectively [78].

DISCUSSION
From the times immemorial, plants have been used as curative agents for variety of ailments.Aegle marmelos preparations are widely available and employed by practitioners of natural health for treatment of diarrhoea, diabetes, inflammation, asthma, fever, ophthalmia, heart problems and to cure poverty of seminal fluid. Most of the studies have been conducted on crude preparations of A. marmelos without mention of their chemical profile. Although the studies of A. marmelos have proved its efficacy in several complications but the detailed research work on isolation of bio actives through clinical trials followed by standardization is seriously required. There have been reports on the clinical uses of A. marmelos which have shown promising results as the plant A. marmelos has a wide array of pharmacological activities and many isolated compounds of A. marmelos lack study on their pharmacological activity.

REFERENCES
1. Kokate CK, Purohit AP, Gokhale SB. Textbook of Pharmacognosy, Edn 20, Nirali Prakashan, Pune (India), 2002, pp. 369.
2. Kokate CK, Purohit AP, Gokhale SB. Textbook of Pharmacognosy, Edn 20, Nirali Prakashan, Pune (India), 2002, pp. 10-11.
3. Kokate CK, Purohit AP, Gokhale SB. Textbook of Pharmacognosy, Edn 20, Nirali Prakashan, Pune (India), 2002, pp. 232.
4. Eisenberg DM, Kesseler RC, Foster C, Norlock FE, Calkins DR, Delbaneo TL. Unconventional medicines in United States. Prevalence, costs and patterns of use. New Engl J Med. 1993; 328: 246-252.
5. Macleanan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicines in Australia. Lancet 1996; 347: 569-573.
6. Parmar C, Kaushal MK. Aegle marmelos Wild fruits, Kalyani Publishers, New Delhi (India), 1982.
7. Nadkarni AK. Dr. Nadkarni’s Indian Materia Medica, Popular Prakashan Co., Mumbai (India), 1986.
8. Kritikar KR, Basu BD. Indian Medicinal Plants, Edn 2, International Book Distributors, Dehradun (India), 1975, pp. 448-502.
9. Jauhari OS, Singh RD, Awasthi RK.  Survey of some important varieties of bael (Aegle marmelos Corr.). Punjab Horticulture J. 1969; 9: 48-63.
10. Pervez MK. Chemisty and pharmacology of some rutaceous plants and marine red and brown algae of Arabian Sea, P.hD. Thesis, Karachi University, 2003.
11. Barthakur NN, Arnold NP. Certain Organic and Inorganic constituents of Bael fruit. Tropical Agriculture (Trinidad), 1989; 66(1): 65-68.
12. Chopra RN, Nayar SL, Chopra IC. Glossary of Indian Medicinal Plants, New Delhi, 1956, pp. 8.
13. Dymock W, Warden H, David H. Pharmacographia Indica, 1890, pp. 277-281.
14. Murugera Mudaliar KS (1988). Materia Medica of Tamil System of Medicine, 1988, pp.221-223.
15. Nadkarni AK. Indian Materia Medica. Edn 3. Popular Press, Mumbai (India), 1976, pp. 23.
16. Anis M, Sharma MP, Iqbal M. Herbal ethnomedicine of the Gwalior Fort Division in Madhya Pradesh, India. Pharmaceutical Bio.2000; 38(4): 241-253.
17. Morton J. Fruits of warm climate. 1987, pp. 187-190.
18. Nadkarni AK. Dr. Nadkarni's Indian materia medica, Popular Prakashan Pvt. Ltd., Mumbai (India), 1992, pp. 203 - 205.
19. Ali MS, Pervez MK. Maemenol: A 7-geranyloxycoumarin from the leaves of Aegle marmelos Corr. Nat. Pdt. Res. 2004; 18(2): 141-146.
20. Wilzer KA, Fronczek FR, Urbatsch LE, Fisher NH. Coumarins from Aster preaealtus, Phytochem. 1989; 28: 1729.
21. Nishioka, T. Isolation and activity of N-p-coumaroyltyramine, an α-glucosidase inhibitor in Welsh onion. Biosci Biotechnol Biochem.1997; 61: 1138.
22. Ulubelen U. A new alkaloid, montainine from Ruta Montana. J Nat Pdt. 1990; 53: 207.
23. Panda S, Kar A. Evaluation of the anti thyroid, anti oxidative and anti hyperglycemic activity of scopoletin from Aegle marmelos leaves in hyperthyroid rats. Phytotherap Res. 2006; 20: 1103-1105.
24. Govindachari TR, Premila MS. Some alkaloids from Aegle marmelos. Phytochem. 1983; 22: 755.
25. Aguirre G, Salgado-Rodriguez A, Flores-Lopez LZ, Parra-Hakka M, Somanathan R. Asymmetric synthesis of naturally occurring β-hydroxamides (R)-Tembamide and (R)-Aegeline. J Mexican Chem Soc. 2001; 45(1): 21-24.
26. Sharma BR, Sharma P. Constituents of Aegle marmelos. II. Alkaloids and Coumarins from fruits. Planta Med. 1981; 43(1): 102-103.
27. Kaur HP, Garg SN, Sashidaran KV, Yadav A. Chemical composition of essential oil of the twigs and leaves of  Aegle marmelos (L.) Correa. J Essen Oil Res. 2006; 16: 144-145.
28. Garg SN, Siddiqui MS, Aggarwal SK. p-Menth-1-en-3β, 5β-diol, A New Constituent of Aegle marmelos leaf, J Essen Oil Res. 1996; 7: 283-286.
29. Goswami S, Gupta VK, Sharma A, Gupta BD. Supramolecular structure of S-(+)-marmesin-a linear dihydrofuranocoumarin. Bull Mater Sci. 2005; 28(7): 725-729.
30. Lampronti I, Martello D, Bianchi N, Borgatti M, Piva R, Jabbar S, Shahbuddin Kabir Chaudhary M, Tareq Hassan Khan M, Gambri R. In-vitro antiproliferative effects on human tumor cell lines of extracts from Bangladeshi medicinal plant Aegle marmelos Correa. Phytomed. 2003; 10: 300-308.
31. Atta-Ur-Rehman, Zareen S, Chaudhary MI, Shaheen F, Pervez M. Conformation of   Imperatorin. Acta Cryst. 2004; E60: o1469-o1462.
32. Manandhar MD, Shoeb A, Kapil RS, Popli SP. New alkaloids from Aegle marmelos. Phytochem. 1978; 17: 1814.
33. Sharma BR, Rattan RK, Sharma P. Marmeline an alkaloid and other components of unripe fruits of Aegle marmelos. Phytochem.1981; 20(11): 2606-2607.
34. Ohnishi T, Suzuki T, Suzuki Y, Ozawa K. A comparative study of plasma membrane Mg+2-ATPase activity in normal, regenerating and malignant cells. Biochem Biophys Acta. 1982; 684: 67-74.
35. Balakrishanan R, Puglendi VK. Influence of umbelliferone on membrane bound ATPases in STZ-induced diabetic rats. Pharmacol Reports 2004; 59: 339-348.
36. Perry LM. Medicinal plants of East and South East Asia. Massachusetts Institute of Technology Press, 1980, pp. 80.
37. Basak KR, Mandal PK, Mukherjee AK. Studies on neutral polysaccharides isolated from bael fruit pulp. Carb Res.1980; 97(2): 315-321.
38. Roiy A, Mukherjee VK, Chintalacharuvu, Rao VN. Structure of   bael gum. Carb Res. 1977; 54(1); 115-124.
39. Mandal PK, Mukherjee AK. Investigation on partial structure of a glycoprotein from bael seed. Carb Res.  1981; 98(1): 85-91.
40. Goel RK, Maity RN, Manickam M, Ray AB. Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa. Indian J Exp Biol. 1997; 35: 1080-1083.  
41. Gridha Shobha F, Thomas M. Studies of anti-diarroheal activity of four medicinal plants in castor oil induced diarrhea. Indian J Pharmacol. 2001; 1: 613-614.
42. Dhuley JN. Investigation on the gastro protective and anti-diarrheal properties of Aegle marmelos Corr. unripe fruit extract. Hindustan Antibiol Bull. 2003; 45-46(1-4): 41-46.
43. Mazumder R, Bhattacharya S, Mazumder A, Pattnaik AK, Tiwary PM, Chaudhary S. Antidiarrhoeal evaluation of Aegle Marmelos (Correa) Linn. root extract. Phytotherap Res. 2006; 20(1): 82-84.
44. Kulkarni KS, Prabhakar B, Irfan S. Efficacy of New Diarex in Diarrhea. Indian Practitioner 2001; 54(7): 497-499.
45. Sachdewa A, Raina D, Srivastava AK, Khemani LD. Effect of Aegle marmelos and Hibiscus rosa sinensis leaf extract on glucose tolerance in glucose induced hyperglycemic rats (Charles foster). J Environ Biol. 2001; 22(1): 53-57.
46. Ponnachan PTC, Paulose CS, Panikkar KR. Hypoglycaemic effect of alkaloid preparation from leaves of Aegle marmelos. Amala Res Bull. 1993; 13: 37–41.
47. Ponnachan PTC, Paulose CS, Panikkar KR. Effect of leaf extract of Aegle marmelos in diabetic rats. Indian J Expt Biol. 1993; 31: 345-347.
48. Upadhya S, Shanbagh KK, Sunneetha G, Balachandra Naidu M. A study of hypo glycaemic and antioxidant activity of Aegle marmelos in alloxan induced diabetic rats. Indian J Phsiol Pharmacol. 2004; 48(4): 476-480.
49. Narender T, Shweta S, Tiwari R, Papi Reddy K, Khaliq T, Prathipati P, Puri A, Srivastava AK, Chander R, Aggarwal SC, Raj K. Anti hyperglycemic and anti dyslipidemic agent from Aegle marmelos. Bioorg Med Chem Lett. 2007; 17(6):1808-1811.
50. Kamalakkannan N, Prince SMP. Hypoglycemic effect of water extract of Aegle marmelos fruit in STZ-induced diabetic rats. J Ethnopharmacol. 2003; 87(2-3): 207-210.
51. Karunanayake EH, Welikinder J. Surmanne SR. Oral hypoglycemic activity of some medicinal plants of Sri Lanka. J Ethnopharmacol. 1984; 11: 223-231.
52. Kesari AN, Gupta RK, Singh SK, Diwakar S, Watal G. Hypoglycemic and anti hyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats. J Herb Pharmacotherap. 2005; 5(3): 87-96.
53. Narendhikaran RT, Subramanian S, Kandaswamy H. Biochemical evaluation of anti diabetogenic property of some commonly used Indian plants on STZ-induced diabetes in experimental rats. J Ethnopharmacol. 2006; 107(3): 374-379.
54. Sabu MC, Kuttam R. Anti diabetic activity of Aegle marmelos and its relationship with its anti-oxidant property. Indian J Physiol Pharmacol. 2004; 48: 81-88.               
55. Anandharajan R, Jaignesh S, Shardanarayanan NP, Viswakarma RA, Balakrishan N. In vitro glucose uptake activity of Aegle marmelos and Syzygium cumini by activation of GLUT-4, P-13 Kinase and PPARγ in L6 myotubes. Phytomed. 2004; 13(6): 434-441.
56. Rajadurai H, Prince PSM. Comparative effects of Aegle marmelos extract and α-tocopherol on serum lipids, lipid peroxidase and cardiac enzymes levels in rats with Isoproterenol induced myocardial infarction. Singapore Med J.  2005; 46(2): 78.
57. Vimal V, Devaki T. Linear furanocoumarins protects rat myocardium against lipid peroxidation and memberane damage during experimental myocardial injury. Biomed Pharmacotherap. 2004; 58: 393-400.
58. Kakiuchi N, Sewaratne LR, Huang SL, Yang XW, Haltai M, Pilapitivaya U, Nambe T. Effects of constituents of Beli (Aegle marmelos) on spontaneous beating and Ca2+ paradox of myocardial cells. Planta Med. 1981; 50: 43-46.  
59. Shankarnathan V, Balakrishanan N, Suresh D, Sureshpardia G, Edwin E. Analgesic activity of methanol extract of Aegle marmelos (Corr.) leaves. Fitoterapia 2007; 78: 258-259.
60. Arul V, Miyazaki S, Ranganathan D. Studies on the anti-inflammatory, anti-pyretic and analgesic property of the leaves of Aegle marmelos Corr. J Ethnopharmacol. 2005; 96: 159-163.
61. Sudharameshwari K, Radhika J. Antibacterial screening of Aegle marmelos, Lawsonia alba and Albizzia libbeck. Afr J Trad Comp Alt Med. 2007; 4(2): 199-204.
62. Dabur R, Singh DD, Gupta A, Mandal TK, Bajpai V, Gaurav AM, Lasekar GS. Antimicrobial activity of some Indian medicinal plants. Afr J Trad Comp Alt Med. 2007; 4(3): 313-318.
63. Balakrishanan N, Bhaskar VH, Jayakar B, Sargameswaran B. Antibacterial activity of Mimosa pudica, Aegle marmelos, Sida cordifolia. Phcog Mag. 2006; 2(7): 198-199.
64. Dubey NK, Mishra AK. Evaluation of some essential oils against dermatophytes. Indian Drugs 1990; 27(10): 529-531.
65. Mishra AK, Dubey NK. Fungiotoxicity of essential of Ammonum subulatum against Aspergillus flavus. Eco Bot. 1990; 44(4): 530-533.
66. Rao BVGN, Joseph PL. Activity of some essential oils towards phytopathogenic fungi. Reischt Aromen Koeperpflengem 1971; 21(11): 405-410.
67. Jain NK. Antifungal activity of essential oil of Aegle marmelos Correa (Rutaceae). Indian Drug Pharma Ind. 1977; 12(1): 55.
68. Begum J, Yusuf M, Chaudhary JU, Wahab MA. Studies of essential oils for their antibacterial and antifungal property. Part 2. Preliminary screening of 35 essential oils, Bangladesh J Sc Indust Res. 1993; 28(4): 25-34.  
69. Pattanaik S, Subramanium VR, Kole C. Antibacterial and antifungal activity of 10 essential oils in vitro. Microbios.  1996; 80 (349): 237-246.
70. Rana BK, Singh UP, Taneja U. Antifungal activity and kinetics of inhibition by essential oil isolated from leaves of Aegle marmelos. J Ethnopharmacol. 1997; 57(1): 29-34.
71. Badam L, Bedekar SS, Sonaware KB, Joshi SP. In vitro antiviral activity of bael upon human coxsackievirus B1-B6. J Communicable Dis. 2005; 34(2): 88-99.
72. Aiyamanthan KEA, Narayanaswamy P. Effect of antiviral principal on rice tungro virus. Indian J Virol. 1998; 4(1-2): 97-99.
73. Lamba B, Bhargava KP. Activity of some synthetic and natural products against experimental ankylostomiasis. Indian J. Pharmacol.1969; 1: 6.
74. Arul V, Miyazaki S, Dhananjayan R. Mechanisms of contractile effect of the alcoholic extract of Aegle marmelos Corr. on isolated guinea pig ileum and tracheal chain. Phytomed. 2004; 11: 679-683.
75. Sur TK, Pandit S, Pramanik T. Antispermatogenic activity of leaves of Aegle marmelos Corr. in albino rats: A preliminary report. Biomed. 1999; 19: 199-202.
76. Sur TK, Pandit S, Pramanik T, Bhattacharya D. Effect of Aegle marmelos leaf on rat sperm motility: An in-vitro study. Indian J Pharmacol. 2002; 34: 276-278.
77. Kar A, Panda S, Bharti S. Relative Efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentration in male mice. J Ethnopharmacol. 2002; 81: 281-285.
78. Jagetia GC, Venkatesh P, Baliga MS. Aegle marmelos (L.) Correa inhibits proliferation of transplanted ehlrich ascites carcinoma in mice. Biol Pharm Bull. 2005; 28(1): 58-64.
79. Jagetia GC, Venkatesh P, Baliga MS. Evaluation of the radio protective effect of Aegle marmelos (L.) Correa in cultured human peripheral blood lymphocytes exposed to different doses of γ-radiation: a micronucleus study. Mutagenesis 2003; 18(4): 387-393.
80. Jagetia GC, Venkatesh P, Baliga MS. Fruit Extract of Aegle marmelos protects mice against radiation-induced lethality. Integrative Cancer Therap. 2004; 3(4):  330-332.
81. Bianchi N, Zuccato C, Lampronti I, Borgatti M, Gambari R. Fetal hemoglobin inducers from the natural world: A novel approach for identification of drugs for the treatment of β-thalassemia and sickle-cell anemia. eCAM. 2009;6(2): 141–151.
82. Sahare KN, Anandhraman V, Meshram VG, Meshram SU, Reddy MV, Tumane PM, Goswami K. Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis. Indian J Exp Biol. 2008; 46(2):128-131
83. Abdul Rahuman A, Gopalakrishnan G, Venkatesan P, Geetha K. Isolation and identification of mosquito larvicidal compound from Abutilon indicum (Linn.) Sweet. Parasitol Res. 2008; 102(5):981-988.
84. Udupa SL, Udupa AL, Kulkarni DR. A comparative study on the effect of some indigenous drugs on normal and steroid-depressed healing. Fitoterapia 1998; 69:507-510.
85. Dahanukar SA, Kulkarni RA, Rege NN. Pharmacology of medicinal plants and natural products. Indian J Pharmacol. 2000; 32:   S81-S118.
86. Gangadhar R, Lalitha Kumari K. Abortifacient activity of the aqueous extract of the leaves of Aegle marmelos in albino rats. Indian Drugs 32; 3: 129—131.
87. Parle M, Bansal N. Antiamnesic Activity of an Ayurvedic Formulation Chyawanprash in mice. eCAM. 2010; 1-10.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


 

Pages

FIND MORE ARTICLES