Bommasani Javali et al, J. Global Trends Pharm Sci, 2018; 9(1): 5020 - 5025

An Elsevier Indexed Journal ISSN-2230-7346

Journal of Global Trends in Pharmaceutical Sciences

REVIEW OF LITERATURE: PHYTOCHEMICAL AND PHARMACOLOGICAL STUDIES ON MUNTINGIA CALABURA Battu Ganga Rao, Jeevitha Konda* , Battu Heera, Bommasani Javali

Department of Pharmacognosy and Phytochemistry, A.U. College of Pharmaceutical Sciences, Andhra University, Viakhapatnam, .

*Corresponding author E-mail: [email protected] ARTICLE INFO ABSTRACT , the family of the rose order (Rosales), with about 3 genera. Key Words The family Muntingiaceae, here described, includes the Neotropical, monotypic genera Muntingia and Dicraspidia, and probably Neotessmannia, which have previously been included in Elaeocarpaceae, , or Muntingia, . Morphological data and molecular data published elsewhere Phytochemical, indicate that none of these families can be regarded as closely related to Pharmacological, these genera. Muntingiaceae belong to a clade that comprises core Muntingiaceae (Sterculiaceae, Tiliaceae, Bombacaceae, and Malvaceae) and several other families. Within this alliance, relationships are presently unresolved. It is native to Western Ghats of India, Malaysia and also found in central and eastern Africa, south-eastern Asia, the , Florida, , Australia, Puerto Rico and many Pacific Islands. It is a large, evergreen , 10-15m in height, indigenous to the evergreen forests at altitude of 450-1,200m and cultivated throughout the hotter parts of India. It requires a soil which is well drained but moist, with a pH of 4.3 to 8.0 and with medium soil fertility. The optimum temperature is 19 to 29c, altitude at approx. Sixteen Hundred meters above sea level and the annual rain fall between 1000 and 2400 mm.

INTRODUCTION: Muntingia calabura is a fast- The are approximately 1.25-2 cm growing slender tree, native to the wide, borne singly or in 2’s or 3’s in the American continent and commonly axils with 5 green sepals and 5 white cultivated in the warm areas of Asian petals and many prominent yellow region. This is a fast-growing tree of stamens. The fruits are abundant, in round slender proportions, reaching a height of shape approximately 7.5-12 m with nearly Taxonomical Classification of Muntingia horizontal spreading branches. The 23 calabura: of M. calabura are evergreen approximately 5-12.5 cm long, alternate Kingdom : Plantae lanceolate or oblong, long pointed at the SubKingdom: Viridiplantae apex, oblique at the base with dark green InfraKingdom: Streptophyta color and minutely hairy on the upper SuperKingdom: Embryophyta surface, gray- or brown-hairy on the Division : Tracheophyta underside and irregularly toothed. Sub Division : Spermatophyta Super order : Rosales

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Order : Malvales core. Fruits are oblong cylindrical in Family : Muntingiacea shape, typically 30-40 cm (12-16 in) in Genus : Muntingia length. Species : calabura Vernacular Names: Bark: The bark is grey, fibrous becomes rough and eventually peeling. English : Jamaican cherry Telugu : Nakkea Regu Traditional Uses: Flowers and bark are Tamil : Tenpazham used as antiseptic to reduce swelling in Kannada : Gasagase hannina mara lower extremities. Leaves either boiled or : Paanchara steeped in water, are used to reduce gastric ulcer prostrate gland swelling and to alleviate headache and cold. Bark Botanical Description: It is a large, decoction is used as a wash to reduce evergreen tree, 10-15m in height, swelling in lower extremities. Infusion of indigenous to the evergreen forests at flowers is used as tonic and tranquillizers, altitude of 450-1,200m and cultivated antispasmodic anti-dyspeptic. The roots throughout the hotter parts of India. are used as emmunoguage and as an abortificient. The leaf infusion is drunk as Leaves: Leaves are dark green, alternate, tea like beaverage. Fruits sometimes eaten entire, simple, glossy, leathery, stiff, large fresh and sometimes cooked as tarts and (up to 16 cm [6 in] in length), and elliptic jams. to oval in form. Leaves are often deeply lobed when juvenile and on young shoots. Past Phyto-chemical Works: Flowers: This species is monoecious, Twelve flavanoids are isolated from having male and female inflorescences (or the M.calabura roots methanolic extract (2S)- "spikes") on the same tree. Male and 5ʹ-hydroxy-7,3ʹ,4ʹ-72 7 trimethoxyflavan, (2S)- female spikes are borne separately on 7,8,3ʹ,4ʹ,5ʹ-pentamethoxyflavan, (2S)-2ʹ- short, stout stems that sprout from older hydroxy- (2S)-8-hydroxy-7,3ʹ,4ʹ,5ʹ- tetramethoxyflavan, (2S)-8,2ʹ-dihydroxy- branches and the trunk. Male spikes are 7,3ʹ,4ʹ,5ʹ- tetramethoxyflavan, (2S)-8,5ʹ- found on younger branches above female dihydroxy-7,3ʹ,4ʹ-trimethoxyflavan, spikes. Male spikes are dense, fleshy, 7,8,3ʹ,4ʹ,5ʹ- pentamethoxyflavone, cylindrical to club shaped, and up to 10 cm (M),(2S),(2ʹʹS)-,(P),(2S),(2ʹʹS)-8,8ʹʹ-5ʹ- (4 in) in length. Flowers are tiny, pale trihydroxy-7,7ʹ-3ʹ,3ʹʹʹ- 4ʹ,4ʹʹʹ-5ʹʹʹ- green when young, turning darker with heptamethoxy-5,5ʹʹ-biflavan, 5ʹ-hydroxy- age. Female flowers are larger, elliptic or 7,8,3ʹ4ʹ-tetramethoxyflavone, (M),(2S),(2ʹʹS)- rounded, with a tubular calyx. The flowers ,(P),(2S),(2ʹʹS)-8,8ʹʹ-5ʹ-5ʹʹʹ-tetrahydroxy-7ʹ,7ʹʹ- are reportedly pollinated by insects and 3ʹ,3ʹʹʹ-4ʹ,4ʹʹʹ-hexamethoxy- 5ʹ,5ʹʹʹ-biflavan, and wind, with a high percentage of 8,5ʹ-dihydroxy-7,3ʹ,4ʹ-trimethoxyflavone. crosspollination. From the leaves of M. calabura, methanolic extract was first partitioned Fruit: Jamaican cherry has a compound or into water, petroleum ether and ethyl multiple fruit (syncarp) with a green to acetate. Only the ethyl acetate partition yellow brown exterior rind that is was further subjected to the isolation composed of hexagonal, bluntly conical procedures, which led to the identification carpel apices that cover a thick, rubbery, of 25 compounds consisting of one new whitish to yellowish wall. The acid to (2R,3R)-7-methoxy-85 3,5,8- sweetish (when ripe) banana flavoured trihydroxyflavanone,) and 24 known flesh (aril) surrounds each seed. The heavy compounds [(2S)-7-hydroxyflavanone fruit is held together by a central fibrous [(2S)-7-hydroxyflavanone, (2S)-5,7- dihydroxyflavanone (pinocembrin),

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Past Pharmacological Works:

Plant Part Used Activity Done Reference Leaves Anti-Diabetic Activity Babu et al., Anti-Inflammatory Activity Karthyaini et al., Anti- Oxidant Activity Ayesha Siddiqua et al., Anti-Microbial Activity William Patrick et al., Anti-Fungal Activity Ramasamy Rajesh et al., Anti- nociceptive Activity ZainulAmiryddin et al., Anti proliferative Activity Zakaria A et al. Fruits and flowers Anti bacterial activity William Patrick et al., Insecticidal activity Orejudos Rubio et al., Anti inflammatory activity Karthyaini et al., Anti-platelet aggregation Chen JJ et al., Root Abortificient Activity Saxena et al., Cardioprotective Activity Nivethetha M et al., Anti hypertensive Activity Shih CD et al.,

(2R, 3R)-3,5,7- trihydroxyflavanone 13 are known compounds 6,7-dimethoxy- (pinobanksin), pinostrobin, 7- 5-hydroxy flavone , 5,7-dimethoxy hydroxyflavone, 5,7-dihydroxyflavone flavone, 3,5-dihydroxy-6,7-dimethoxy (chrysin), 3- methoxy-5,7,4ʹ- flavone, (2S)-5ʹ-hydroxy-7,8,3ʹ,4ʹ- trihydroxyflavone (isokaemferide), 3,3ʹ- tetramethoxy flavane, β-sitostenone, 6β- dimethoxy-5,7,4ʹ- trihydroxyflavone, 3,8- hydroxystigmast-4-en-3-one, β-sitosterol, dimethoxy-5,7,4ʹ-trihydroxyflavone, 3,5- syringic acid, vanillic acid, 3-hydroxy-1- dihydroxy- 7,4ʹ-dimethoxyflavone (3,5-dimethoxy-4-hydroxyphenyl)propan- (ermanin), 3,5-dihydroxy-7,8- 1- one, tetracosyl ferulate, and, a mixture dimethoxyflavone (gnaphaliin), 5- of 1-tetracosanol and 1- hexacosanol. hydroxy-3,7,8-trimethoxyflavone, 5,4ʹ- dihydroxy-3,7,8-dimethoxyflavone, 5- CONCLUSION hydroxy-3,7,8,4ʹ-tetramethoxyflavone, Muntingia calabura is an 2ʹ,4ʹ-dihydroxychalcone, 4,2ʹ,4ʹ- evergreen tree belonging to family trihydroxychalcone (isoliquiritigenin), 7- Muntingiacea, which is commonly known hydroxyisoflavone, 7,3ʹ,4ʹ- as Jamaican Cherry. The phytochemical trimethoxyisoflavone (cabreuvin), (2S)-5ʹ- evaluation of Muntingia calabura revealed hydroxy-7,8,3ʹ,4ʹ-tetramethoxyflavan, the presence of various constituents such 2ʹ,4ʹ-dihydroxydihydrochalcone, 3,4,5- as Flavanoids, Flavanones, Biflavanoids trihydroxybenzoic acid, lupenone, and and Steroids. Many other compounds with 2α,3β-dihydroxy-olean-12-en-28-oic acid. their active chemical constituents have Methanol extract of M. calabura been discussed. The pharmacological stem bark was partitioned between H2O- studies shown Anti-diabetic, Anti- CHCl3 prior to the isolation processes, inflammatory, Anti-ulcer, Hepato where the CHCl3-soluble fraction was protective, Anti-oxidant, Insecticidal, Anti collected for the isolation purposes. fungal, Abortificient, Anti proliferative, Isolation procedures carried out on the and Cytotoxic properties. CHCl -soluble fraction led to the 3 ACKNOWLEDGEMENT: identification of 15 compounds of which two are new compounds 8-hydroxy- The authors are thankful to Prof. B. 7,3ʹ,4ʹ,5ʹ- tetramethoxy flavone and 8,4ʹ- Ganga Rao , Head , Pharmacognosy and dihydroxy-7,3ʹ,5ʹ-trimethoxy flavone and Phytochemistry, A. U. College of

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Pharmaceutical Sciences, Visakhapatnam, of action as potential for his valuable suggestions throughout the chemotherapeutic agents. In: Rao research work and for helping us V, ed. Phytochemicals - A Global throughout. Perspective of Their Role in Nutrition and Health. Rijeka, REFERENCES: Croatia: InTech Europe, 1-32. DOI: 10.5772/26052. 1. Babu PV, Liu D, Gilbert ER. 9. Duke JA. (2009). Duke’s (2013). Recent advances in Handbook of Medicinal of understanding the anti-diabetic Latin America. Boca Raton, FL: actions of dietary flavonoids. J CRC Press. Pp.469-470. González- Nutr Biochem 24: 1777-1789. Lamothe R, Mitchell G, Gattuso Balan T, Mohd Sani MH, 2. M, Diarra MS, Malouin F, Bouarab 2. Suppaiah V, Mohtarrudin N, K. (2009). Plant antimicrobial Suhaili Z, Ahmad Z, Zakaria ZA. agents and their effects on plant (2013). and human pathogens. Int J Mol 3. Antiulcer activity of Muntingia Sci 10: 3400-3419. calabura leaves involves the 10. Huen MSY, Leung JWC, Ng W, modulation of endogenous nitric Lui WS, Chan MNS, Wong JTF, oxide and nonprotein sulfhydryl Xue H. (2003). 5,7-Dihydroxy-6- compounds. Pharm Biol 52: 410- methoxyflavone, a benzodiazepine 418. Bandeira GN, C. da Camara site ligand isolated from AG, de Moraes MM, Barros R, Scutellaria baicalensis Georgi, Muhammad S, Akhtar Y. (2013). with selective antagonistic 4. Insecticidal activity of M. calabura properties. Biochem Pharmacol 66: extracts against larvae and pupae of 125-132. diamondback, Plutella xylostella 11. Ibrahim IAA, Abdulla MA, (Lepidoptera, Plutellidae). J King Abdelwahab SI, Al-Bayaty F, Saud Univ Sci 25: 83–89. Majid NA. (2012). Leaves extract 5. Chen JJ, Lin RW, Duh CY, Huang of Muntingia calabura protects HY, Chen IS. (2004). Flavones and against gastric ulcer induced by cytotoxic constituents from the ethanol in Sprague-dawley rats. stem bark of Muntingia calabura. J Clin Exp Pharmacol S5: 004. Chin Chem Soc 51: 665-670. doi:10.4172/2161-.S5-004 143 6. Chen JJ, Lee HH, Shih CD, Liao 12. ICRAF (International Center for CH, Chen IS, Chou HT. (2007). Research in Agroforestry) (2004). New dihydrochalcones and anti- Muntingia calabura [Online]. platelet aggregation constituents Available at:Janick J, Paull RE. from the leaves of Muntingia (2008). The Encyclopedia of Fruit calabura. Planta Med 73: 572-577. and Nuts. Oxfordshire, OX: CAB 7. Chen JJ, Lina WJ, Shieha PC, International. Chen IS, Peng CF, Sung PJ. 13. Kaneda N, Pezzuto JM, Soejarto (2010). A new long-chain alkene DD, Kinghorn AD, Farnsworth constituents from the leaves of NR. (1991). Plant anticancer Muntingia calabura. Chem 1401 agents, XLVIII. New cytotoxic Biodivers 7: 717-721. flavanoids from Muntingia 8. Craig WJ. (1997). Phytochemicals: calabura roots. J Nat Prod 54: Guardians of our health. J Am Diet 196-206. Assoc 97: 199- 204. Doughari JH. 14. Karthyaini, Suresh K, (2012). (2012). Phytochemicals: Extraction Pharmacognostic evaluation, in methods, basic structures and mode

5023

Bommasani Javali et al, J. Global Trends Pharm Sci, 2018; 9(1): 5020 - 5025

vitro antioxidant and in vivo anti- 23. Schmeda-Hirschmann G, Yesilada inflammatory studies of Muntingia E. (2005). Traditional medicine and calabura Linn. J Global Trends gastroprotective crude drugs. J Pharm Sci 3: 805-811. Ethnopharmacol 100: 61-66. 15. Katzung BG, Masters SB, Trevor 24. Shih CD, Chen, Lee HH. (2006). AJ. (2012). Basic and Clinical Activation of nitric oxide signaling Pharmacology (12th Edition). pathway mediates hypotensive LANGE Basic Science. McGraw- effect of Muntingia calabura L. Hill Medical, New York, NY, (Tiliaceae) leaf extract. Am J Chin USA. Med 34: 857-872. 16. Liu Q, Fang D, Zheng J. (2004). 25. Shih CD. (2009). Activation of Solvent effects on infrared spectra nitric oxide/cGMP/PKG signaling of methyl 4- hydroxybenzoate in cascade mediates pureorganic solvents and in antihypertensiveeffects of ethanol/CCl4 binary solvents. Muntingia calabura in anesthetized Spectrochim Acta Part A 60 spontaneously hypertensive rats. 17. Meyer BN, Ferrigni NR, Putnam Am J Chin Med 37: 1045-1058. JE. (1982). Brine shrimp: A 26. Yasunaka K, Abe F, Nagayama A, convenient general bioassay for Okabe H, Lozada-Perez L, Lopez- active plant constituents. Planta Villafranco E, Muniz EE, Aquilar Med 45: 31-34. A, Reyes-Chilpa R. (2005). 18. Mitchell SA, Ahmad MH. (2006). Antibacterial activity of crude A review of medicinal plant extracts from Mexican medicinal research at the University of the plants and purified coumarins and West Indies, Jamaica, 1948–2001. xanthones. J Ethnopharmacol 97: W Indian Med J 55: 243-269. 293-299. 19. Morton JF. (1987). Jamaica cherry. 27. Yob NJ, Mohd. Joffry S, Meor In: Morton JF, ed. Fruits of Warm Mohd. Affandi MMR, Teh LK, Climates. Miami, Florida 2: 65-69. Salleh MZ, Zakaria ZA. (2011). 20. Nivethetha M, Jayasari J, Brindha Zingiber zerumbet (L.) Smith: A P. (2009). Effects of Muntingia review of its ethnomedicinal, calabura L. on isoproterenol- chemical and pharmacological induced myocardial infarction. J uses. Evid Based Complement Med Singapore 50: 300-302. Alternat Med 2011 Article ID 21. Preethi K, Vijayalakshmi N, 543216, 2011. Shamna R, Sasikumar JM. (2010). DOI:10.1155/2011/543216. In vitro antioxidant activity of 28. Yusof MM, Teh LK, Zakaria ZA, extracts from fruits of Muntingia Ahmat N. (2011). Antinociceptive calabura Linn.from India. Phcog J activity of the fractionated extracts 2: 11-18. of Muntingia calabura. Planta Med 22. Sani MH, Zakaria ZA, Balan T, 77: PF21. doi: 10.1055/s 0031- The LK, Salleh MZ. (2012). 1282409. Antinociceptive activity of 29. Zakaria ZA, Sulaiman MR, Jais methanol extract of Muntingia AMM, Somchit MZ, Jayaraman calabura leaves and the KV. (2006a). The antinociceptive mechanisms of action involved. activity of Muntingia calabura Evid Based Comp Altern Med aqueous extract and the 2012: Article ID 890361. involvement of L-arginine/nitric doi:10.1155/2012/890361. oxide/cyclic guanosine monophosphate pathway in its

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Bommasani Javali et al, J. Global Trends Pharm Sci, 2018; 9(1): 5020 - 5025

observed activity in mice. Fundam AK, Zuraini A, Somchit MN. Clin Pharmacol 20: 365-372. (2010). In vitro antimicrobial 30. Zakaria ZA, Fatimah CA, Jais activity of Muntigia calabura AMM, Zaiton H, Henie EFP, extracts and fractions. Afr J Sulaiman MR, Somchit MN, Microbiol. Thenamutha M, Kasthuri D. 37. Zakaria ZA, Mohamed AM, Jamil (2006b). The in vitro antibacterial NSM, Rofiee MS, Hussain MK, activity of Muntingia calabura Sulaiman MR, Teh LK, Salleh extract. J Pharmacol 2: 290-293. MZ. (2011). In vitro 31. Zakaria ZA, Jais AMM, Mastura antiproliferative and antioxidant M, Jusoh MSH, Mohamed AM, activities of the extracts of Jamil MNS, Rofiee MS, Sulaiman Muntingia calabura leaves. Am J MR. (2007c). In vitro Chin Med 39: 1-18. 1580 antistaphylococcal activity of the 38. Zakaria ZA, Kumar GH, Zaid extracts of several Muntingia SNH, Ghani MA, Hassan MH, calabura in Malaysia. J Pharmacol Hazalin NAMN, Khamis MH, 3: 428-431. Devi GR, Sulaiman MR. (2007a). 32. Zakaria ZA, Hassan MH, Aqmar Analgesic and antipyretic actions NMNH, Ghani MA, Zaid MSNH, of Muntingia calabura leaves Sulaiman MR, Kumar GH, chloroform extract in animal Fatimah CA. (2007d). Effects of models. Orient Pharm Exp Med 7: various nonopioid receptor 34-40. antagonist on the antinociceptive 39. Zakaria ZA. (2007b). Free radical activity of Muntingia calabura scavenging activity of some plants extracts in mice. Methods Find Exp available in Malaysia. J Clin Pharmacol 29: 515-20. Pharmacol Ther 6: 87-91. 33. Zakaria ZA, Mustapha S, Sulaiman 40. Sibi G, Naveen R, Dhananjaya K, MR, Jais AMM, Somchit MN, Ravikumar KR, Mallesha H. Fatimah CA. (2007e). The (2012). Potential use of Muntingia antinociceptive action of aqueous calabura L. extracts against human extract from Muntingia calabura and plant pathogens. Pharmacogn leaves: The role of opioid J 4: 44-47. receptors. Med Prin Pract 16. 34. Zakaria ZA, Hazalin NAMN, Zaid SNHM, Ghani MA, Hassan MN, Gopalan HK, Sulaiman MR. (2007f). Antinociceptive, anti- inflammatory and antipyretic effects of Muntingia calabura aqueous extract in animal models. J Nat Med. 35. Zakaria ZA, Somchit MN, Sulaiman MR, Jais AMM, Fatimah

CA. (2008). Effects of various receptor antagonists, pH and enzymes on Muntingia calabura antinociception in mice. Res J Pharmacol 36. Zakaria ZA, Sufian AS, Ramasamy K, Ahmat N, Sulaiman MR, Arifah

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