February 2017 Available Online on ISSN 2249-9954

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954

Detail Study on Simarouba glauca (DC) Plant for its Medicinal Importance - A Review

1 2 3 Iyyappan Arivu* , Minnady Muthulingam ** , Rathinam Palaniappan

1.*Ph.D., Department of Zoology, Faculty of science, Annamalai University, Tamilnadu, India- 608 002

2. **Assistant Professor, Department of Zoology, Faculty of science, Annamalai University, Tamilnadu, India-608 002.

3. Ph.D., Department of Zoology, Manonmaniam Sundaranar University, Tamilnadu, India- 627 012

Abstract Simarouba glauca (Family: Simaroubaceae) is a medium sized evergreen tree begins to bear fruits, when it is 6-8 years old and attains stability in production after another 4-5 years. The flowering is annual, beginning in December in India. The trees are polygamodioecious and only some females are heavy bearers. By grafting with a suitable scion in situ the sex of the plant can be transformed as desired and the productivity can be increased. The drupelets turn black or greenish yellow when they are ready for harvest during April/May. Manually harvested drupelets are depulped, washed and sun-dried and transported at convenience for processing. The main active groups of chemicals in Simarouba glauca are called quassinoids, which belong to the triterpene chemical family. Quassinoids are found in many plants and are well known to scientists. The antiprotozoal and antimalarial properties of these chemicals have been documented for many years. Several of the quassinoids found in Simarouba glauca, such as ailanthinone, glaucarubinone, and holacanthone, are considered the plant's main therapeutic constituents and are the ones documented to be antiprotozal, anti-amebic, antimalarial, and even toxic to cancer and leukemia cells. The main plant chemicals in simarouba include: ailanthinone, benzoquinone, canthin, dehydroglaucarubinone, glaucarubine, glaucarubolone, glaucarubinone, holacanthone, melianone, simaroubidin, simarolide, simarubin, simarubolide, sitosterol, and tirucalla. This paper include the evidence based overview of pharmacological and phytochemical properties of the Simarouba glauca, which may very use full to establish a standard natural drug for feature and further research for various purpose.

Keywords: Simarouba glauca, Quassinoids, Pharmacology, Phytochemistry.

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954

Introduction

The World Health Organization estimates that 80% of the world's inhabitants rely mainly on traditional medicines for health care (Gurib- Fakim 2006). Natural products and their derivatives have historically been exploited as a valuable source of novel therapeutic agents (Koehn FE and Carter 2005). Plants as natural medicines to benefit humans have a long history and ancient civilization, particularly in some nations such as India, China, Egypt, and Greece. The majority of world populations still rely on plant based medicine because of several reasons such as long history of safe use, affordability and easy availability. The growing interest in drugs of plant origin may also be due to several other reasons such as a large section of world's population does not have access to conventional pharmacological treatment and side effects and other problems of synthetic drugs due to incorrect use.

Natural product remains a prolific source of discovery of new drugs from the ancient Vedic period. India has long history of management of human health through Ayurveda which came in to existence more than 6000 yrs ago. Charak and Sushurt had contributed a lot in the development of plant based medicine and surgery. In recent years, there has been growing interest in complementary medicine, functional and therapeutic uses of natural products, especially those derived from plants. Thus, natural products including terrestrial and marine plant extracts have become a source of optimism for drug discovery. The rich biodiversity of India has attracted the attention of researcher, which remained untouched as far as the new drug discovery is concerned (Srivastava 2013).

Simarouba glauca (Figure-1) also has a long history in herbal medicine in many other countries. An infusion of the leaves or bark is considered as astringent, digestive, anthelmintic, and emmenagogue. It is taken internally for diarrhea, dysentery, malaria, and colitis; it is used externally for wounds and sores. There the bark and, occasionally, the roots are boiled in water to yield a powerful astringent and tonic used to wash skin sores and to treat dysentery, diarrhea, stomach and bowel disorders, hemorrhages, and internal bleeding. In Brazil it is employed much the same way against fever, malaria, diarrhea, dysentery, intestinal parasites, indigestion, and anemia. In high dosages it is reported to be emetic, diuretic, and soporific. In Brazilian herbal medicine, Simarouba glauca bark tea has long been the most highly recommended (and most effective) natural remedy against chronic and acute dysentery. After a 200-year documented history of use for dysentery, its use for amoebic dysentery was finally validated by conventional doctors in 1918. A military hospital in England demonstrated that the bark tea was an effective treatment for amoebic dysentery in humans (Shepheard 1918).

In India it grown well in the wastelands of Orissa, Karnataka and Gujarat. Besides, Andhra Pradesh, Bihar, Chhattisgarh, Maharashtra and Tamil Nadu are potential states where it can be grown successfully. However, there are less privileged geographical regions in North Eastern Dry Zone of Karnataka, which receive low and erratic rainfall that cannot support good vegetation. Cultivation of traditional crops adopting recommended packages is very much uneconomical and often disastrous to formers in these regions. Several measures are suggested for mitigating this problem. Since agriculture is not sustainable, the farmers want to take Simarouba glauca plantation on the bunds as well as the block plantation on farm lands. Among them, recommending a low cost input technology for cultivating Simarouba glauca that can

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954 grow well even with erratic and low rainfall, still giving assured returns is of great significance (Devaranavadgi et al., 2005).Indian government have to take immediate action to save formers life with economical cultivation particularly formers are suicide every day because of water scarcity to maintain the vegetation this year November and December unfortunately we lost our natural gift as a rainfall very low amount we got. If its increasing in feature the total agricultural place will be destroyed many useful medicinal plants like Simarouba glauca will be endanged species list. Therefore it’s our concern to conserve medicinal plants for next generation.

Figure1. Simarouba glauca

Simarouba glauca tree Simarouba glauca leaves

Simarouba glauca ripped fruits Simarouba glauca seeds

Distribution in India: It was first introduced by National Bureau of Plant Genetic Resources in the research station at Amravati in Maharashtra in 1966 and to the University of Agricultural Sciences, Bangalore in 1986. In India it is cultivated in Orissa, Maharashtra and also at introductory stage of plantation in other states like Anand (Gujarat) Jodhpur (Rajasthan) Andhra Pradesh, Karnataka, Tamilnadu, West Bengal and Bhubaneswar (Orissa) (Joshi and Joshi, 2002). Systematic Research and developmental activities on Simarouba glauca began from 1992 onwards (Joshi and Joshi, 2002). Now the cultivation of Simarouba glauca spread to semiarid dry and saline land areas of other Indian states like Gujarat, Tamilnadu, Maharashtra, Karnataka

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954 and Andhra Pradesh. Simarouba glauca tree has an ability to grow well even in marginal wastelands or dry land with degraded soil (Govindaraju et al., 2009).

Common Names: Paradise Tree (English) Sorgamaram (Tamil), Lakshmitaru and Shorgum maram (Malaiyalam), Ainta, Bilchuli, Hartho (Hindi) and other names are Simarouba, gavilan, negrito, maruba, dysentery bark, bitterwood, palo blanco, robleceillo, caixeta, daguilla, cedro blanco, caju-rana, malacacheta, palo amargo, pitomba, bois amer, bois blanc, bois frene, bois negresse, simaba .

Phytochemistry: Simarouba glauca containing large number of such compounds as alkaloids, flavonoids, carbohydrates, glycosides, phenolic compound, tannins, triterpenoids, cardinolides, saponins, fixed oils as described in literatures Ailanthinone, benzoquinone, canthin, dehydroglaucarubinone, glaucarubine, glaucarubolone, glaucarubinone, holacanthone, melianone, simaroubidin, simarolide, simarubin, simarubolide, sitosterol, tirucalla (Kokate 2000, Khandelwal 2009, Kumar et al., 2009).

Pharmacological and Biological activity: Amoebicide, analgesic, anthelmintic, antibacterial, antidysenteric, antileukemic, antimalarial, antimicrobial, antitumorous, antiviral, astringent, cytotoxic, emmenagogue, febrifuge, skin hydrator, stomachic, sudorific, tonic, vermifuge, hepatoprotective activity, antidiabetic activity, Anti-inflammatory activity.

Uses of paradise tree: All parts of the plant namely, seed, shell, fruit pulp, leaf, leaf litter, unwanted branches, stem, bark, and root generate products that are useful in the production of food, fuel, manure, timber, medicine etc.

Food oil: Simarouba glauca seeds contain 60-75% oil that can be easily refined, bleached, deodorized and fractionated. It is suitable for edible and non-edible purposes.

Edible uses: The oil is extracted from the seeds in the existing oil mills and processed by adopting conventional methods. Each well-grown tree yields 15 to 30 kg nut lets equivalent to 2.5-5 kg oil. This amounts to nearly 1000-2000 kg oil/ha/year (400-800 kg/acre/year) (with 500 plants/ha; 200 plants/acre).

Antinutritional composition: Literature survey on toxic and antinutritional factors of Simarouba meal indicated that very scanty literature pertaining to identification and estimation of different toxic and anti nutritional factors in Simarouba glauca meal is available , systematic study was conducted by Severen, 1953, Vaughan, 1970, Rath et al.,1987. Studies of Govindaraju et al., (2009) indicated that deoiled meal of S. glauca is rich source of protein (47.7 g/100g) with high solubility (92%), in vitro protein digestibility (88%)and amino acid based computed nutritional indices, They revealed after identification and estimation of toxic constituents that Simarouba glauca meal required detoxification from saponin (0.95g/100g), alkaloid (1.01g/100g), phenolics (0.95g/100g) and phytic acid (0.73g/100g) before its usage potential could be utilized in feed/ food formulations.

Govindraju et al., (2009) further reported that proteins of Simarouba glauca meal show relatively in vitro digestibility of 88%. They speculated that high in vitro protein digestibility in

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954

Simarouba glauca meal could be attributed to lower tannin levels, which inhibit the trypsin digestion. Further Simarouba glauca protein might not be bound to minor constituents by glycosidic or ester linkages making it easily digestible. Considering the high protein content of Simarouba glauca meal (~ 48g/100g) investigations carried out by Govindraju et al., 2009 on its different quality characteristics in order to determine the potential of its usage as feed or food. Their result indicates that protein solubility profile of Simarouba meal as a function of PHC followed ‘U’ pattern which is typical of oilseed proteins. Simarouba glauca seed protein had solubility minima (23.7%) and iso-electric precipitation at PH 4.0 on the other hand, the Simarouba glauca proteins showed maximum solubility (92%) at PH 9.0. Typical protein solubility profiles with similar solubility values were reported by Wang et al., 1999; Rakshit and Bhagya 1988 and Vinay and Sindhukanya 2008 for rice bran, Jatropha and Karanja Proteins respectively. To identify different anti nutritional factors in Simarouba meal related to quassine.

Studies of Govindaraju et al., (2009) indicated that of the methanolic extract of Simarouba meal gave purple mauve color with anisaldehyde in sulphuric acid, for the presence of saponins. They had purified saponins; the methanolic extract of Simarouba glauca meal was passed through ion exchange column, using di-ion HP2O resin colorimetric determination indicated that Simarouba glauca meal contained 3.7g/100g total saponins. They subjected Saponins from Simarouba glauca meal, to Lieberman-Burchard reaction, using acetic acid and sulphuric acid gave pink color. This indicated that aglycone portion of saponin is triterpenoid type. They speculated that saponins are amphiphilic compounds, in which sugars are linked to nonpolar group (Sapogenin), which may be either a sterol or a triterpene. Their studies on haemolytic activity indicated potent haemolysis in samples of Simarouba glauca saponins. Samples of Simarouba saponins in 0.9% saline they reacted with erythrocytes and haemoglobin released were measured at 540 nm. They showed that crude saponin of Simarouba was comparable to haemolysis; whereas purified saponin of Simarouba glauca was much more potent in haemolysis, showing HD5O value at 0.5-0.60mg/ml compared to HD50 value of soy saponin at 1.20- 1.40 mg/ ml (Patil Manasi and Gaikwad 2011).

Anticancerous Activity: Antitumor /Antileukemic Activity The quassinoids glaucarubinone and alianthinone demonstrated in vitro antitumor activity. The quassinoids glaucarubinone and dehydroglaucarubinone have demonstrated activity in vitro towards murine leukemia and murine lymphocytic leukemia P38 (Valeriote 1998).The bark and leaf extract of Simarouba glauca is well known for its different types of pharmacological properties are not only anticancerous but also haemostatic, antihelmentic, antiparasitic, antidysenteric, antipyretic activity (Patil and Gaikwad 2011). The chloroform soluble extract of Simarouba glauca exhibited significant cytotoxicity against several human cancer cell lines (Likhitwitayawuid et al., 1993, Seo et al., 2001). Morre et al., Studied the mode of action of Simarouba glauca in antitumor activity, the plasma membrane-associated NADH oxidase of transformed cells was shown to be inhibited by nanomolar and sub nanomolar concentrations of the antitumor quassinoid, glaucarubolone. The inhibition was seen with plasma membrane vesicles of HeLa cells at two log orders less glaucarubolone than with plasma membrane vesicles of rat liver. Assignment of a drug-binding site to the external surface of the HeLa cell plasma membrane was supported by findings where full activity of the glaucarubolone in the inhibition of NADH oxidase activity of isolated plasma membrane vesicles and of growth of HeLa cells was given on a molar glaucarubolone basis by

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954 an impermeant conjugate of glaucarubolone in which the glaucarubolone moiety was linked via the C-15 hydroxyl to amino polyethyleneglycol (ave Mr 5,000). The activity of the conjugate, and to a lesser extent, of free glaucarubolone was modulated by the redox environment of the cells and of the plasma membrane vesicles. Activity, both in the inhibition of NADH oxidase activity and in the inhibition of growth, was enhanced by oxidizing conditions in the presence of oxidized glutathione compared to reducing conditions in the presence of reduced glutathione.

Cytotoxic Activity: An ethanol-water extract of Simarouba glauca root demonstrated cytotoxic activity towards human oral epidermoid carcinoma Ca-9KB at ED50<20 mcg/ml. A water extract of the seeds showed activity towards the same tumor cell line at ED50<20 mcg/ml. A water extract of the bark was cytotoxic at 10% towards human cervical adenocarcinoma (hela) cells (May 1978).

Antimalarial activity: Chloroform and water extracts of the wood, bark and twigs of Simarouba glauca demonstrated strong antimalarial activity when given orally or subcutaneously to chickens infected with Plasmodium gallineceum. Active doses given ranged from 1.5 mg/kg - 500 mg/kg (Spencer 1947). A chloroform and methanol extract of the fruit was active against chloroquine resistant Plasmodium falciparum; the methanol extract was active at IC50=0.05 mcg/ml. In mice the methanol fruit extract given orally at 900 mg/kg was active towards Plasmodium berghei (O’Neill 1988). In another study Simarouba was active in both chloroquine-susceptible and resistant forms of Plasmodium berghei in mice. (Franssen 1997). Antimicrobial, antiamebic and antiprotozoal activity is attributed to the quassinoids. (Wright 1993) In malaria the quassinoids are able to inhibit protein synthesis and nucleic acid synthesis in human erythrocytes infected with Plasmodium falciparum (Kirby 1989).

Antibacterial activity: Antibacterial activity of three different concentrations of extracts of Simarouba glauca has been evaluated in vitro against gram positive and negative bacteria that are known to cause infections in humans and plants. The extracts showed varying degrees of antimicrobial activity against tested microorganisms. Methanol extracts exhibited higher degrees of antibacterial activity than the other extracts. Ethyl acetate extracts showed least inhibition of growth of microorganisms. The inhibitory effects of the extracts were compared with the standard antibiotics such as cefotaxime (Lakshmi et al., 2014). In vitro antibacterial activities were examined for chloroform, methanol and ethyl acetate extracts. Antibacterial activities of plant leaf extracts against five pathogenic bacteria (one Gram positive and four Gram negative) were investigated by the well diffusion methods. Agar plates were inoculated with 100 μL of standardized inoculums (1.5 x 108 CFU/mL) of each selected bacterium (in triplicates) and spread with sterile swabs. Wells of 6 mm size were made with sterile borer into agar plates containing the bacterial inoculums and the lower portion was sealed with a little molten agar medium. The sets of three dilutions (10, 25 and 50 μg/mL) of plant leaves extracts (chloroform, methanol and ethyl acetate solvent) were poured into a different well of inoculated plates (Lakshmi et al., 2014).

Industrial purposes: Its seeds contain about 40 % kernel and kernels content 55 -65% oil. The amount of oil would be 1000 – 2000 kg/ha/year for a plant spacing of 5m x5m. It was used for industrial purposes in the manufacture of soaps, detergents and lubricants etc. The oil cake being

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954 rich in nitrogen (7.7 to 8.1%), phosphorus (1.07%) and potash (1.24%) could be used as valuable organic manure (Joshi et al., 2001).

Biodiesel from Simarouba glauca: Simarouba glauca was a rich source of fat having melting point of about 290C. The major green energy components and their sources from Simarouba glauca were biodiesel from seeds, ethanol from fruit pulps, biogas from fruit pulp, oil cake, leaf litter and thermal power from leaf litters, shell, unwanted branches etc. Unlike fossil fuels, biodiesel is a renewable source of energy, because it comes from biological sources like plants and animals which can be replenished by farming. (Okoro et al., 2011). On the other hand, fossil fuels come from underground deposits of hydrocarbons which cannot be renewed. Biofuels have become a matter of global importance because of the need for an alternative energy at a cheaper price and with less pollution.

Ramadhas et al., (2005) studied Biodiesel was a domestic, renewable fuel for diesel engine comprised of mono-alkyl esters of long chain fatty acids derived from natural oils/ vegetable oils/animal fats designated as B100 and which meets the specification of ASTM D6751 or BIS IS15607:05. It was obtained by the transesterification of renewable materials composed of C14 – C20 fatty acids triglycerides with short chain alcohol such as methanol or ethanol under the presence of catalyst, usually a base like NaOH or KOH. Instead of using alcohol and catalyst separately, alkoxides such as CH3ONa or CH3OK were used to reduce tendency to from water. Biodiesel was often referred to as fatty acid methyl esters (FAME) when methanol was used. The Glycerol was produced as a by-product which has commercial value.

Biodiesel has become more attractive to replace the petroleum fuels. As per reputed literature, most of the transestrification studies have been done on edible oils like rapeseed, soybean, and sunflower etc by using NaOH or KOH catalyst. (Mishra et al., (2012) The tree borne oil like Simarouba glauca is the most potential species to produce biodiesel in India which could offer opportunity the generation of rural employment therefore it’s really fortunate to our peoples and many study need to improve the production of alternative fuels from Simarouba glauca.

Benefits to economy: Lot of the waste lands are elaborating in the world because of climatic changes therefore it is very suitable to get microeconomics level farmers, owning the marginal and wastelands in semi-arid zones, start getting some income after five years of planting. They get a regular income of Rs 65,000/ha/year (Rs 20,000 from nutlets + Rs 25,000 from timber +Rs 20,000 from vermicompost) (Rs.26, 000/acre/year), from 10th year onwards, regardless of vagaries in rainfall pattern. At macroeconomics level, nations attain self-sufficiency in the production of edible, industrial oils, biofuels and timber on a long-term basis. Cultivation of Simarouba glauca saves huge amount of foreign exchange every year by solving the energy crisis to a considerable extent.

Benefits to society: Particularly in employment generation in agricultural field, Simarouba cultivation generates on farm employment to crores of farmers (365 labor days/ha) especially rural women (about 80%). The establishment of industries such as oil, biofuel, timber, particleboard, activated charcoal etc. in the rural areas, generates agro-industry based off-farm employment in the villages. At global level, Simarouba glauca project provides livelihood to

International Journal of Advanced Scientific and Technical Research Issue 7 volume 1, January –February 2017 Available online on http://www.rspublication.com/ijst/index.html ISSN 2249-9954 about 30% of the population. Simarouba glauca cultivation helps in the poverty alleviation of unemployed farmers owning unproductive lands all over the world.

Conclusion We conclude from above review the plant Simarouba glauca which is having wide range of value not only medicinal value but also lot of the benefits to the society due to variety of chemical constituents can be further investigated on toxicological and other study of mode of action, histological, parameters to obtain a valuable marketed product. Apart from that the chemical constituents, who were found effective can also be synthetically prepared for better yield and obtain a pharmacophore which may be useful for drug design.

Acknowledgment

The authors grateful to Dr. N. Indra, Professor of Zoology and Sethupathy, Professor and Head, Department of Biochemistry, Rajah Muthiah Medical College and Hospital, Annamalai University for providing facilities.

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