Chemical and Pharmacological Aspects of Toona (Meliaceae)

The genus Toona belongs to family Meliaceae is a group of traditionally important medicinal plants. Toona is commonly known as toon, the leaves, barks and roots of toon is commonly used as herbal medicine and also as timber. Extensive research works have been carried out on chemical constituents and biological activities of the genus Toona. In this review, we summarize previous and current information regarding chemical constituents and biological activities of the genus Toona and provide new insights for future study in this discipline. This study shows that Toona species posses several biological activities mainly due to the presence of coumarins, flavonoids, phytosterol, phenols, tenins, alkaloids, triterpenes and anthraquinons.

INTRODUCTION

In 1840, Toona was originally described by Endlicher as a section of Cedrela. Later Roemer in 1846 recognized that it could be separated by a number of sound morphological characters, raising Toona to generic rank. Thus, the old world species of Cedrela were transferred to Toona (Roemer, 1846). The genus Toona (Meliaceae) consists of upland trees that are widely distributed at the higher altitude eastwards from India, Nepal, China, Burma, Thailand, Malaysia, Java to Europe (Edmonds and Staniforth, 1998). About 15 species are found in tropical Asia and Africa, while only 4 species are found in India among them 2 species T. serreta and T. hexandra are found in north west Himalaya. The leaves of Toona sinensis (A. Juss.) Roem are used as vegetable in Tiwan. Its leaves and stems are also used as a carminative and to treat enteritis, dysentery and itch in oriental medicine. Toona species are mainly timber yielding plants and well known for their medicinal properties. These are deciduous trees upto 30 m high. Toona serrata (Royal) M. Roem. is commonly used in the treatment of ulcers and asthma (Gaur, 1999). Phytochemical screening of Toona has been done for retinoid, vitamins, coumaric acid, kaempferol, methyl gallate, quercetin, afzelin, quercitrin, isoquercitrin, rutin, cedrellin and phytol derivatives (Park et al., 1994, 1996; Luo et al., 2000). The antiangiogenic and antidiabetic activities of rutin and vitamin C were studied using in vivo as well as in vitro models (Guruvayoorappan and Kuttan, 2007; Alsaif, 2009). The purpose of this review is to collect all the possible information regarding the chemical constituents and biological effects of the genus Toona, thus will help to the researchers and scientists to take action for future study in this discipline. However, the literature survey revealed that no work has been done on the quantification of bioactives and mineral elements of Toona species by RP-HPLC, HPTLC and ICP-MS, respectively, In the field of natural products analysis, HPLC has gained acceptance as an analytical technique, especially for separation of complex mixtures of secondary constituents.

CHEMICAL CONSTITUENTS

Traditionally, chemical constituents of Toona are extracted into ethanol or methanol, after which the solvent was removed by vacuum distillation. The bioactives were separated by column chromatography on silica gel using different ratio of n-hexane: EtOAC, CHCl₃: MeOH and EtOAC:MeOH (Hsieha et al., 2006; Zhao et al., 2009) with increasing polarity as a mobile phase (Fig. 1). High performance liquid chromatography is the most important method of choice for the separation of bioactives of Toona. Both normal phase and reverse phase columns have been used.

Fig. 1:	Structure of isolated compounds from Toona

Table 1:	Distribution, chemical constituents, biological activities and traditional uses of Toona species

However, RP-HPLC with C₁₈ columns and gradient elution (MeOH:H₂O) seems to be the most preferred method (Zhao et al., 2009). Distribution, chemical constituents, biological activities and traditional uses of Toona species are shown in Table 1.

A number of compounds including retinoid, vitamins B and C, coumaric acid, kaempferol, methyl gallate, quercetin, afzelin, quercitrin, isoquercitrin, rutin, cedrellin and phytol derivatives have been isolated from this plant (Park et al., 1994, 1996; Luo et al., 2000). Kaempferol, catechin, epicatechin and Polyphenol Contents also isolated and identified from Torreya grandis, Swietenia macrophylla and Indigofera Species (Saeed et al., 2007; Falah et al., 2008; Bakasso et al., 2008). Methanolic extract of Toona ciliata showed carbohydrate, coumarin glycoside, flavinoids, phytosterol, phenols and tenins (Gautam et al., 2010). Phytochemical investigations showed that the leaves of T. sinensis were rich in flavonoids, alkaloids, terpenes and anthraquinones (Chen et al., 2000; Persnol et al., 2001). Polyphenols including methyl gallate, gallic acid, kaempferol, quercitin, quercitrin, rutin, kaempferol-glucoside, catechin, epicatechin, stearic acid, palmitic acid, sitosterol, stigmasterol, sitosteryl-glucoside and stigmasteryl glucoside have been determined in Toona sinensis by Micellar Electrokinetic capillary Chromatography (MEKC) method, using UV detection (Hsieh et al., 2006). Phytochemical work on the Toona species has led to the isolation of triterpenes and phenolic compounds (Paula et al., 1997; Mulholland and Taylor, 1992; Benencia et al., 1999; Veitch et al., 1999; Segura et al., 1994; Hsieh et al., 2004). 3-Acetoxy-17-furan-3-yl-1-hydroxy-1,4,4,10,13-pentamethyl-12-oxo-tetradecahydro-16,20-dioxa-cyclopropa [14,15] cyclopenta [alpha] phenanthrene-7-carboxylic acid methyl ester, beta-sitosterol, stigmasterol , palmitinic acid, 3-(3-Propyl-[1,1',3',1"]-tercyclohexan-3"-yl)-propan-1-ol were isolated from petrol and chloroform extracts of Toona ciliata (Li et al., 2009).

Shao-Hong (2010) were studied the inhibitive effects of ethanol extract of Toona ciliata leaves on protein non-enzymatic glycation end products formation. The essential oils (sesquiterpenes) of T. ciliata have been analyzed by GC-MS. The oils from the leaves (0.05%, v/w) and stems (0.05%, V/W) of T. ciliata contained 36 and 31 components (Maia Beatriz et al., 2000). Liao et al. (2007) isolated norlimonoids and limonoids from the leaves and stems of T. ciliata. 12-Deacetoxytoonacilin and 6α-acetoxy-14α,15α-epoxyazadirone have been isolated from the seeds of T. ciliata (Neto et al., 1995). Mu et al. (2007) determined volatile compounds in T. sinensis by MAE-HS-SPME followed by GC-MS. Tirucallane-type triterpenoids, pimaradiene-type diterpenoid and limonoids were isolated from the leaves and twigs of T. ciliata. Toonaciliatone, methyl-3α-acetoxy-1-oxomelic-14(15)-enate, perforin A and cholest-14-ene-3,7,24,25-tetrol-21,23-epoxy-21-methoxy-4,4,8-trimethyl-3-(3-methyl-2-butenoate) were isolated from the leaves of T. ciliata (Ning et al., 2010). 12-α-Hydroxystigmast-4-en-3-one was isolated from the petroleum ether extract of T. ciliata together with two steroids and three C-methyl coumarins (Chowdhury et al., 2003a). Cedrelone, a tetranortriterpenoid, isolated from T. ciliata on photolysis by UV light yielded a true 14 beta, 15beta, 22beta, 23beta-diepoxy-6-hydroxy-1,5, 20(22)-meliatriene-2,7,21-trione (Gopalakrishnan et al., 2000). Lignans, flavonoids and cholestane were isolated from T. microcarpa (Fang et al., 2010). 21-Hydroxycedrelonelide, 23-hydroxycedrelonelide, limonoids, cedrelone, 23-hydroxytoonacilide, sitosterol, α-amyrin and α-amyrin acylated with fatty acids, coumarins, siderin, scopoletin and isofraxidin were also isolated (Vilela, 1994). Cedrellin, 2,6,10,15-phytatetraene-14-ol, 7α-obacunyl acetate, 6-acetoxyobacunol acetate, 7α-acetoxydihydronomilin, 2,6,10-phytatriene-1,14,15-triol and phytol were isolated from leaves of Cedrela sinensis (Luo et al., 2000). The eight mineral elements (Ca, P, Mn, Zn, Ni, Fe, K and Mg) have been detected in Cedrela toona by AAS (Vermani et al., 2010). Tetranortriterpenoids have been isolated from Toona sureni (Kraus and Kypke, 1979). Methyl gallate, exhibited potent antioxidant activity has been isolated from the leaves of Toona sureni (Ekaprasada et al., 2009). Five triterpenes (Cedrelone, Piscidinol A, Niloticin, Bourjotinolone A, 3-Episapelin A) were isolated from EtOAc extract of the leaves of Toona sureni, some of them showed significant antiplasmodial activity (Cuong et al., 2007).

BIOLOGICAL ACTIVITIES

Bark, oil, seed, flower and leaf of Toona have been used in traditional Chinese medicine. The leaves of T. sinensis were used medicinally for the treatment of heliosis, vomitting, dysentery, detoxification and antiinflammation (Wang et al., 2007). Chang et al. (2002) reported that T. sinensis possess antiproliferative effect and also promote the apoptosis of human lung cancer cell. Liao et al. (2006) showed that the scavenging activities of leaves, roots and barks of T. sinensis extract were over 80% at a concentration of 0.625 mg mL^-1. Antifatigue activity of water extract of T. sinensis have been determined by Feng et al. (2009). T. sinensis is used for the treatments of enteritis, dysentery and itch in oriental medicine (Edmonds and Staniforth, 1998; Oiano-Neto et al., 1998). The leaf extract of T. sinensis was found to have an evident effect against Severe Acute Respiratory Syndrome (Chen et al., 2008). Glucosidase inhibitory constituents were isolated from the stems of T. sinensis (Zhao et al., 2009). Toonaciliatin showed moderate antifungal activity against Trichophyton rubrum with an MIC of 12.5 μg mL^-1 (Chen et al., 2009). The crude extracts and a major isolate, siderin, obtained from the petroleum ether extract of T. ciliata were found to exhibit significant cytotoxicity (Chowdhury et al., 2003). Hypoglycemic effects of T. sinensis have also been reported. Flavonoid of T. sinensis decreased the blood glucose levels of alloxan induced diabetic mice (Zhang et al., 2008). 12-alpha-hydroxystigmast-4-en-3-one was found cytotoxic in a brine shrimp lethality bioassay with LC 50 of 9.9 μg mL^-1 and it also showed significant antitumor activity (Chowdhury et al., 2003b).

The extract of T. ciliata along with siderin, a major coumarin from T. ciliata, exhibited significant in vitro antibacterial activity (Chowdhury et al., 2003a). The extract of T. sinensis and gallic acid was found to possess effective antioxidant activity against various oxidative systems in vitro (Hseu et al., 2008). Extract of T. sinensis exhibited antiproliferative and antitumorigenic activities (Yang et al., 2010). The ethanol extract of T. ciliata Roemer (heart wood) showed anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer (antisecretory), HCl-ethanol induced ulcer (cytoprotective) and water immersion stress induced ulcer in rats. The researchers reported that T. ciliata extract at a dose of 300 mg kg^-1 p.o. markedly decrease the incidence of ulcers in all these three models. The plant extract also showed gastro protective activity (Malairajan et al., 2007). T. sinensis have been investigated for its potent anti-inflammatory and analgesic effects (Chang et al., 2002). Gallic acid was identified as the major anti-cancer compound in T. sinensis leaf extracts. It is cytotoxic to DU145 prostate cancer cells (Chen et al., 2009). Antioxidant activity of the methanol and water extracts of Chinese toon (Toona sinensis) has been evaluated using DPPH radical scavenging and lipid peroxidation assays (Cheng et al., 2009). Feng et al. (2009) have evaluated the antifatigue activity of water extracts of T. sinensis Roemor leaf. Such type of work have been published by the group previously (Negi et al., 2009, 2010a-c; Bhandari et al., 2010).

CONCLUSION

High Performance Liquid Charomatography (HPLC), Capillary Electrophoresis (CE), Micellar Electrokinetic Capillary Chromatography (MEKC) and column charomatography are to be able to provide a rapid separation and high resolution of the principal polyphenols of Toona. Toona species possess several biological activities such as antifatigue, antifungal, cytotoxicity, hypoglycemic, antidiabetic, antibacterial, antioxidant, anti-ulcer, gastro protective, anti-inflammatory, analgesic, anti-cancer and antiproliferative, mainly due to the presence of coumarins, flavinoids, phytosterol, phenols, tenins, alkaloids, triterpenes, steroid and anthraquinons. Isolation, separation, characterization and quantification of bioactives from some species of Toona are in progress.

ACKNOWLEDGMENTS

The authors are thankful to Dr. Asha Budakoti, NCL, Pune and Dr. D.S. Rawat, Delhi University, Delhi for providing some references and Chemdraw software.