Ethnomedicinal, Antimicrobial and Antidiarrhoeal Studies on the Mangrove Plants of the Genus Xylocarpus: A Mini Review

Plants and plant based metabolites are widely used in ethnomedicinal practices around the world. Plants are rich in wide variety of secondary metabolites such as tannins, terpenoids, alkaloids, flavonoids, flanonoids, phonolics, glycosides, saponins, and steroids etc. which have been used for treatment of various diseases for ages. Like any other plant communities, the mangrove plants have also been reported for there ethnomedicinal uses. Mangroves are the unique plant communities inhabiting the estuarine and intertidal regions of both tropical and subtropical coasts are largely confined to the region between 30° north and south of the equator. These are salt tolerant plant communities comprising of trees, herbs, shrubs and grasses. There are about 39.3 million acres of mangrove forests in the warm coastlines of tropical oceans all over the world distributed in 112 countries and territories [1]. Out of the given total mangrove species and their associates, the number of exclusive or true mangrove species in the world is 68 and they belong to 27 genera. Approximately 55 species of mangroves from 22 genera were distributed in Indian Ocean region [2]. These plants inhabit an extremely challenging environmental abiotic stress condition enumerated by high salinity, water logging condition, high and low tides of water, high temperature, low oxygen, low nutrition, muddy anaerobic soil and strong wind conditions where other plants cannot grow. Along with these abiotic stress factors, the insects and microorganisms and other anthropological condition also contribute a large in developing the biotic stress to these unique plant community. However, these mangrove plants adapted well to these ecological hostile condition by alterations in their physiological processes resulting in the synthesis of novel chemical compounds that offer protection to these plants against various biotic and abiotic stresses mentioned above [3]. A number of these phytocompounds or secondary metabolites have significant pharmacological properties are being used traditionally for treatment of number ailment [4].


Introduction
Plants and plant based metabolites are widely used in ethnomedicinal practices around the world. Plants are rich in wide variety of secondary metabolites such as tannins, terpenoids, alkaloids, flavonoids, flanonoids, phonolics, glycosides, saponins, and steroids etc. which have been used for treatment of various diseases for ages. Like any other plant communities, the mangrove plants have also been reported for there ethnomedicinal uses. Mangroves are the unique plant communities inhabiting the estuarine and intertidal regions of both tropical and subtropical coasts are largely confined to the region between 30° north and south of the equator. These are salt tolerant plant communities comprising of trees, herbs, shrubs and grasses. There are about 39.3 million acres of mangrove forests in the warm coastlines of tropical oceans all over the world distributed in 112 countries and territories [1]. Out of the given total mangrove species and their associates, the number of exclusive or true mangrove species in the world is 68 and they belong to 27 genera. Approximately 55 species of mangroves from 22 genera were distributed in Indian Ocean region [2]. These plants inhabit an extremely challenging environmental abiotic stress condition enumerated by high salinity, water logging condition, high and low tides of water, high temperature, low oxygen, low nutrition, muddy anaerobic soil and strong wind conditions where other plants cannot grow. Along with these abiotic stress factors, the insects and microorganisms and other anthropological condition also contribute a large in developing the biotic stress to these unique plant community. However, these mangrove plants adapted well to these ecological hostile condition by alterations in their physiological processes resulting in the synthesis of novel chemical compounds that offer protection to these plants against various biotic and abiotic stresses mentioned above [3]. A number of these phytocompounds or secondary metabolites have significant pharmacological properties are being used traditionally for treatment of number ailment [4].
For centuries, mangroves have been traditionally used for food (fruits and nectar), feed and medicinal purposes in different parts of the world. They are well known to produce natural metabolites with diverse biological activities. Several mangrove plants viz. Acanthus ilicifolius, Aegiceras majus, Avicennia africana, A. marina, A. officinalis, Ceriops caudolleana, Exocoecaria agallocha, Kandelia rhecdi, Nypa fruticans, Rhizophora mangle, R. mucornata and Sonneatia caseolaris are widely used by local medical practitioners in many countries like Africa, South East Asia, South America and Australia including India. These plants are used to cure some diseases like leprosy, elephantiasis, tuberculosis, malaria, dysentery, ulcers and some skin diseases [5]. The mangroves plants are reported to contain some unique class of diverse compounds that includes phorbol esters, phenolics and related compounds, steroids, triterpenes, and their glycosides, tannins, other terpenes and related compounds, flavonoids, tannins, anthocyanins, alkaloids etc [3]. A number of these compounds or secondary metabolites have significant medicinal properties that can be exploited in shaping better human health care needs.

Botanical Features
The genus Xylocarpus consists of trees growing around littoral of the tropical Indian Ocean and extending to the Pacific Islands distributed widely in the coastal areas of South-East Asia, Australia and East Africa [15]. The genus Xylocarpus belonging to the family Meliaceae has three distinct species in India viz. Xylocarpus granatum (Koenig), X. moluccensis (lamk.) and X. mekongensis Pierre [16]. However, it has been reported that another species i.e. X. rumphii belonging to the genus Xylocarpus genus inhabits sandy and rocky seashores in the tropics like Srilanka, Malaysia and some parts of Australia [17]. Out of these four species, X. rumphii appears to be less common in distribution and abundance. X. granatum commonly known as a 'cannon ball tree' is a large spreading medium mangrove tree growing in inter-tidal silty clay soil, with rounded coriaceous leaves, smooth thin bark, and abundant red heartwood forming well developed buttresses surrounding the trunk base. Mature fruits hang on the mother plants almost throughout the year. Diameter of the fruit is up to 20 cm or slightly more, yellowish brown fruit coat, completely round with long woody stalk. X. moluccensis is a medium-sized crooked, much branched ever green tree up to 10 m tall growing generally on the sandy or rocky bay, away from the frequent tidal inundation. They are found on the fringes of backwater creeks. They have pointed leaves, deeply serrated bark and an undistinguished timber. The fruit is the size of a mandarin orange of 5-7 cm in diameter. The X. mekongensis is a medium sized tree that grows generally on the inter-tidal silty but consolidated clay or on the sandy or rocky bay. The plant has well developed aerial blunt end pneumatophores or root suckers. It has green coloured fruit of diameter generally not exceeding 15 cm. The morphological features and distribution of these plants have been summarised in (Table 1).

Ethnomedicinal Reports
Ethnomedicine refers to the study of traditional medicinal uses practised by different ethnic groups in concerned with the cultural interpretation of health, diseases and illness. The practice of ethnomedicine involves written documents, experience and knowledge that have been shared from generation to generation [18]. The ethnomedicinal study plays a vital role in drug discovery and anthropological research. It constitutes the scientific backbone for developing active therapeutics based on traditional medicines of different human indigenous societies.
Ethnomedicinal studies on X. granatum have been documented by several researchers. It has been reported that extracts of different parts of X. granatum are used traditionally as relief for fever including malaria, inflammation, dysentery, cholera and other abdominal problems in certain parts of the globe [19,20]. Different extracts of roots, barks [3], fruit seed coat, seed kernels [21] are used to treat cholera and treatment of diarrhoea.
X. mekongensis, another species of the genus Xylocarpus has been reported to have ethnomedicinal uses. The bark and pneumatophore of X. mekongensis possess antimalarial, antidiarrhoeal and antinociceptive activities [3,22,23]. Traditionally X. mekongensis is used as an astringent and in the treatment of fever, dysentery, diarrhoea [24]. The kernel root of this plant also reported for their anti-inflammatory properties [25].
Yet another species of the genus Xylocarpus i.e. X. moluccensis is also used in traditional medicinal practices as reported by several studies. The fruit and bark of X. moluccensis is used in the treatment of fever, malaria, antidiarrhoea, antiemetic, elephantiasis and swelling of the breast etc. [3]. An ointment prepared from seed ash of the plant X. moluccensis along with sulphur and coconut oil is used for treatment of itch [24]. The ethnomedicinal uses of the different species of the Xylocarpus plants have been summarized in (Table 1).

Phytochemical Constituents
The mangrove plants that belong to the genus Xylocarpus have shown enormous ethno medicinal potential; however, few reports are available about their active principles responsible for their biological activities. The presence of alkaloids, flavonoids, monoterpnes, triterpenoids, tetratriterpenoids, limonoids, phenolic acids, steroids etc. has been reported in the leaves, stem bark and fruits of these plants [3,19]. Numerous alkaloids have been reported in the barks, roots and fruits extracts of X. granatum [26]. Four alkaloids viz. N-methyl flindersine, chelerythrine, dihydrochelerythrine, acetonyl dihydrochelerythrine were isolated from the root barks of X. granatum [27]. Besides, its fruits also contain many alkaloids like xylogranatinin, granatoin [28][29][30]. Flavonoids like catechin, epicathechin, kaempferol, 3-O-β-D-glucoside are found in different parts (bark, fruits and leaves) of the plant X. granatum [19,28,31]. Similarly, the bark of X. moluccensis is reported to contain flavonoids like catechin and epicatechin [19]. X. granatum seeds are rich source of limonoid xylocarpin [32] and hispidol B [26]. Its bark is rich in gedunin, xyloccensins L-V, 6-dehydroxyxylocarpin D [19,[33][34][35][36][37]. Several limnoids viz. Xyloccensin (A-I), Xylocarpin, Humilin B are also reported in bark and leaves extracts of X. moluccenesis [32]. The presence of four novel tetranotriterpenoids named xylogranatins A-D (1-4) with have been demonstrated by phytochemical exploration of seed extracts of X. garanatum [38]. The seeds of X. granatum plant have been reported to contain rich sources of tirucallane-type triterpednoids [39]. These plants are also reported to have many compounds of limonoids from its different species that include Gedunin group, Andirobin group, Mexicanolide group and Obacunol group [40]. The mangroves X. granatum and X. moluccenesis are distinguished for producing antifeedant limonoids especially mexicanolides and phargmalins. Recently Protoxylogranatin, a new derivative of phargmalins has been isolated from X. granatum which plays a pivotal role in oxidative cleavage in biogenetic pathway to limonoid [41]. X. granatum leaves are rich in cholesterol, campestrol,

Page 3 of 7
Antimicrobial and Antidiarrhoeal Activities of Xylocarpus Sp.

Antimicrobial activity
The phytochemicals as remedy for various ailments including microbial infections have been known for centuries which form the basis for their use in ethnomedicinal practices around the world [59]. Recently, the indiscriminate use of antibiotiotics has led to the emergence of multidrug resistant microbial strains; hence the search for novel antimicrobial compounds is the need of the hour.
The antibacterial property [66,67] of the different species of the mangrove genus Xylocarpus can be attributed to the presence of different secondary metabolites like flavonoids, saponins, polyphenols. Some important antimicrobial phytochemicals isolated from the mangrove plants of genus Xylocarpus have been included in (Figure 1).

Antidiarrhoeal activity
According to WHO census for developing nations, diarrhoea remains a major cause of infant mortality and morbidity [68]. Though various drugs are available for treatment of diarrhoea still numerous side-effects (e.g. abdominal discomfort, dry mouth, nausea, constipation and headache) are associated with these drugs. In comparison to conventional drugs, numerous herbal antidiarrhoeal remedies from various medicinal plants are available having lesser side effects and better efficacy. The bioactive compounds from these plants exert their antidiarrhoeal activity by decreasing the gastrointestinal motility as well as the secretions in vivo [69]. Phytoconstituents like tannins, tannic acid, flavonoids, alkaloids, sesquiterpenes,
It has been reported that the extracts of different parts of two Xylocapus species such as X. granatum and X. moluccensis are traditionally used for treatment of diarrhea. The ethanolic bark and leaves extracts of X. granatum showed antidiarrhoeal activity in number diarrhoeal animal models. They were found to exhibit significant antidiarrhoeal activity in a dose dependent manner [62]. The purging indices and percent purging indices for bark extracts of X. granatum were reported to be 32.09, 22.75% (500 mg/kg) and 14.07, 10.30% (1000 mg/kg) and for leaves extract as 51.56, 40.66% (500 mg/ kg) and17.62, 28.83% (1000 mg/kg) respectively. The decreased percent purging indices represent the potential antidiarrheal activity of bark and leaf extracts. In another experiment, the methanol extracts of X. granatum bark has been reported for their antidiarrhoeal activities in experimental castor oil and magnesium sulphate induced by diarrhoeal mice. The methanol extract showed dose-dependent antidiarrhoeal activity in both models at 250 and 500 mg/kg dose as evident by reduced number of faeces and total number of diarrhoeic faeces. The antidiarrhoeic activity of these extracts may be due to antisecretory mechanism, decreased water reabsorption or delayed gastrointestinal transit [11]. Lakshmi et al. [70] also reported that fruit seed coat of X. garantum showed promising antidiarrheal activity at 500 mg/kg dose level in castor oil induced diarrhoeal mice model. The ethanol extracts of the fruit on further fractionation leads to isolation of many bioactive molecules [71] like gedunin, photogedunin, palmitic acid as listed in (Table 4).
Another species of the mangrove plant that belongs to the Xylocarpus genus i.e. X. moluccensis is also reported for it's antidiarrhoeal activities. The methanol bark extracts of X. moluccensis exhibited significant antidiarrhoeal activity in castor oil and magnesium sulphate induced diarrheal mice models at 250 and 500 mg/kg doses [21,22]. Structures of some important antidiarrhoeal compounds isolated from Xylocarpus plants have been included in (Figure 2).

Possible Mechanism of Action
Although there are very few reports are available on the on the isolated compounds from the Xylocarpus species, but assumptions can be made about the possible mechanism of action of these mangrove isolates on their antibacterial and antidiarrhoeal activities. The Xylocarpus plants are known for the occurrence of a characteristic compound called limonoids that have a wide spectrum of biological activities, particularly insecticidal action [72]. Some of the other phytochemical compounds such as glycosides, saponins, tannins, flavonoids, terpenoids, and alkaloids are also reported to have antimicrobial activity [63,73]. The phytochemical screening of these Xylocarpus plants have shown the presence of diverse class of compounds like alkaloids, terpenoids, tannins, glycosides, saponins, steroids, coumarins etc. which may be responsible for its antimicrobial activities against a wide range of microbes including Gram positive and Gram negative bacteria, yeast, fungi [60].
Diarrhoea is usually a result of gastrointestinal infection, which can be caused by a variety of bacterial, viral and parasitic organisms. Further, disturbances in the transport of electrolytes and water in the intestines give rise to diarrhoea leading to increased luminal osmolarity, increased electrolyte secretion, decreased electrolyte absorption and deranged intestinal motility causing a decreased transit time [73]. Studies on X. granatum, and X. moluccensis revealed that these plants are rich in potential antidiarrhoeal bioactive compounds like tannins, tannic acid, flavonoids, alkaloids, sesquiterpenes, diterpenes, terpenes and terpenoids [21] that can be utilized in antidiarrhoeal drug development [69]. The complex content of chemicals derived from these plants may have multiple targets of action and might therefore have several potential effects against diarrhoeal disease. The involvement of synergistic effects of astringent and antibacterial effect in combination with decreased intestinal movements might be responsible for their antidiarrhoeal potentials.

Future Prospects and Conclusion
The mangrove plants inhabit a unique ecological habitat exemplified by various stress conditions like high salinity, water logging, low oxygen condition, light stress, low nutrition conditions are reported to be biochemically unique and possess several bioactive compounds. Compounds isolated from the mangrove species have the potential to act as lead compounds for drug discovery. The different mangrove species of Xylocarpus possess significant pharmacological activities which can be pharmaceutically exploited. These plants have shown promising therapeutic applications in treatment of various ailments particularly in microbial infection and diarrhoea as reported by various ethnomedicinal and experimental studies. Even though extracts from mangroves and mangrove-associated species possess therapeutically activity moieties against a number of diseases, the specific metabolites responsible for these bioactivities are remained to be elucidated.

The bioactive compounds isolated from mangrove plants like
Xylocarpus have advantages over the conventional medicines as the ethnomedicinal studies suggested that the diversified chemical content from these plants have multiple targets of action and might therefore have several potential therapeutic effects against diarrhoeal diseases. The involvement of synergistic effects of astringent and antibacterial effect of these plant extracts in combination with decreased intestinal movements may play vital role for their antidiarrhoeal potentials. However, safety, adverse effects and toxicity assays of these plant products has to be carried out in order to have a basis of these mangrove plant species to be recommended as phytomedicines useful against diarrhoea. Though many plants have been used in folklore medicine worldwide, recently, extracts from mangroves and their associated species have been proven to possess antimicrobial activities against a number of human, animal and plant pathogens.
The information presented in this review clearly indicates that the different mangrove species of Xylocarpus viz. X. granatum, X. moluccensis and X. mekogenesis possess pharmacologically active compounds such as alkaloids, flavonoids, limonoids, terpenoids, phenolic glycosides etc. having enormous therapeutic potential in alleviating a number of ailments. However, bioactivity guided isolation of these phytoconstituents is needed to establish the activity-structure relationship that may reveal the bioactive compounds responsible for different pharmacological activities in general and antimicrobial and antidiarrhoeal activities in particular.