Almost all parts of the plant are used as folklore remedy for the treatment of various ailments of Indian traditional healers, but the leaves are of particular interest from a medicinal point of view⁽³⁾as an anti-diarrheal⁽⁴⁾ , Hepatoprotective,⁽⁵⁾anti- inflammatory⁽⁶⁾anti- tussive, anti-pyretic, anti- ulcer drug, among other parts^(3,7). In spite of its significant traditional medicinal value, this plant has not been explored extensively till now with respect to pharmacognostical, traditional use, phytochemical and therapeutic parameters. The present attempt is to review and compile updated information on the above mentioned aspects of FH. This article will help to enhance the existing knowledge of Ficus hispida and will also create awareness of the possible new therapeutic uses for the development of pharmaceutical entities for the better health care in the near future.

Taxonomical classification⁽⁸⁾

Domain: Eukaryote

Kingdom: Plantae

Division: Magnoliopsida

Order: Rosales

Family: Moraceae

Genus: Ficus

Species: hispida

Common names:

Ficus Hispida, derived from Latin word FIK-us “for Fig” and HISS-pih-duh” with bristly hairs, is commonly known as devil fig, hairy fig, opposite-leaved fig-tree and rough- leaved fig. in India is been recognised by many diferent names in different languages like in Gujrati as umbar; Hindi as gobla, kagsha, kalaumbar, katularia, phalgu; Kannada as advaiatti, kadaatti; Konkani as kharvoti; Malayalam as erumanaakk, kaattaththi, paarakam; Marathi as bokeda, bokhada, bokheda, dhedumbar, karavati; Sanskrit as kakodumbrika, malayuhu, phalgu, phanika; Tamil as peyatti; and Telugu as bomma-medi. Apart from India, it is widely known as hpauwu, kadut, kha-aung, mai-nawt-hpu in Burmese, dui yet rong in Chinese, kota dimbula in Sinhalese, and ma duea plong in Thai. Other synonyms which are commonly used are Covellia hispida (Linnaeus f.) Mique; Ficus compressa S.S. Chang; F. Heterostyla Merrill; F.letaqui H. Liveilh and Vaniot; F. Sambucixylon H. Livelily⁽⁹⁾.

Morphology:

The height of the tree is about 10 meters and it is a coarsely hairy shrub or medium sized tree. It grows in secondary forests, open lands and river banks, up to 1200 m in altitude⁽³⁾. Bark is generally brownish or blaze pink with lantecellate. Shape of leaves is simple, decussate, ovate, oblong, or obovate-oblong. And they are thickly papery, covered with coarse hairs and oppositely arranged on 1-4 cm long petiole; lamina 7-35 x 3-16 cm (40 x 18 cm in saplings); is narrow elliptic-oblong, ovate and obovate with rounded subcordate or truncate-subcordate base; margin is entire or dentate, sometimes irregularly toothed, scabrid on bothsurfaces and hispid beneath having acute to mucronate apex; midrib is three-nerved at base; secondary nerves are four to nine pairs, often branched, ascending; tertiary nerves broadly reticulo-percurrent. Ovate-lance shaped spitules are usually four in number and are visible on leafless fruiting branches and sometimes on pendulous leafless branches^(10).Male flowers are many and found near apical pore; calyx is three lobed, thinly membranous; stamen 1. Gall flowers: calyx is absent; style subapical, short and thick. Female flowers: calyx lobes absent; style lateral with hairs appearing during the months of June and July⁽¹¹⁾. Figs appear in leaf axil on normal leafy shoots, sometimes on leafless branchlets, solitary or paired, yellowed or red when mature, top shaped and 1.2-3 cm in diameter.

Microscopy ⁽⁴⁾

The fruit has a single layered epidermis covered with thick cuticle having a few unicellular trichomes. Collenchymatous cells are present in the epidermis which is by four to six layers and is hexagonal to polygonal in shape. Rosette crystals of calcium oxalate are present in few cells; mesocarp is composed of large, oval to polygonal, thick walled parenchymatous cells; a few vascular vessels show spiral thickening. Cork consisting of thin-walled are present in the roots which are 5-10 layers, compressed cells, with outer layers exfoliating; irregularly arranged is the cortex zone, tangentially elongated, thin walled, parenchymatous cells, some of which contain rosette crystals of calcium oxalate and dark red coloured contents; secondary phloem consists of usual elements compromising thin-walled cells; cellulosic phloem fibers are found scattered throughout the secondary phloem in singles and in groups of two or three; a few phloem parenchyma and phloem ray cells contain rosette crystals of calcium oxalate; secondary xylem is situated centrally, consisting of usual elements, all being lignified; xylem vessels are numerous and equally distributed the secondary xylem region, in singles as well as in groups of two to six; xylem rays are numerous, straight and one to five cells wide.

Extraction methods:

Since ages, the tribals from Assam and Manipur are using the extracts of leaves, bark and roots of Ficus hispida in the treatment of jaundice⁽¹²⁾and diabetes⁽¹³⁾. The extraction methods for these plant parts are well documented in the literature and supported by various scientists. Dhanasekaram et.al, prepared the methanolic extract of powdered dried leaves by extracting it with methanol on water bath (50^oc). The solvent was removed by filtration and fresh solvent was added to the plant material. This process was repeated twice. Storage of the obtained extract was done at 0-4^oc for further use ⁽¹⁴⁾. Sometimes independently some workers adopted a slightly different approach of first defatting the dried leaves using petroleum ether (60-80ml) and then extracting and then extracting with methanol^(15,16,17). Ghosh et al, ground the dried bark and extracted it with double distilled ethanol and isolated the water soluble portion ⁽¹⁸⁾. The extraction from roots was carried out by a method similas to that used by Dhanasekaram et al ⁽¹⁹⁾ with leaves.

Phytochemistry:

Preliminary phytochemical investigations of ficus hispida have shown the presence of alkaloids, carbohydrates, proteins and amino acids, sterols, phenols, flavanoids, gums and mucilage, glysocides, saponins and terpenes⁽¹⁴⁾. Previous reports by Acharya et al, show that Ficus hispida bark contains lupeol acetate, beta- amyrine acetate, and beta-sitosterol. In another study, purification of acetates of n-tricontanol, beta-amyrin and gluanol was carried out from the petroleum ether extracts of the dried bark powder⁽²⁰⁾. S. Wang and D. A.Coviello obtained a new and unusual compound, 10-ketotetracosyl arachidate, when the bark was extracted with light petroleum^(21,22). Venkatachalam et al, isolated two substantial phenanthroindolizidine alkaloids, 6-O-methytylophorinidine and 2-demethoxytylophorine, a novel biphenylhexahydroindolizine hispidin from the stem and leaves of Ficus hispida⁽²³⁾. Recently, hispidin has been reported to have anti cancer activity⁽²⁴⁾. Peraza-Sanchez etal, revealed the occurrence of known phenanthroindoliziline alkaloid, n-alkanes, coumarins and triterpenoid and identified anew norisoprenooid ficustriol from the methanolic extract of leaves and twigs of this plant⁽²⁵⁾. Recently, Hong et al, demonstrated that leaves contain hispidin, oleonalic acid, bergaptine, beta-amyrine and beta-sitosterol⁽²⁴⁾. Quishi Song et al, implicated the presence of a number of volatiles from the fruit, that include linalool, linalool oxide, terpeneol and 2,6-dimethyl-1,7-octadiene-3,6-diol, which may act 7as the attractants of the wasps responsible for pollination of Ficus hispida⁽²⁶⁾.

Pollination biology of Ficus hispida ⁽²⁷⁾

For propagating descendants, the fig and fig pollination wasps are completely dependent on each other. They are highly co-evolved mutalists. Fig wasps are the main reasons for pollination in all fig species. The fig wasps are developed only in fig syconia. Ficus hispida being a dioecious tree which blossoms annually and bears fruit 6-8 times and hence 4-5 fruit bearing peak. The male trees produce pollen and provide fig wasps with reproductive havens, while the female trees produce fig seeds after pollination by the female wasps. Pollen of Ficus hispida cannot escape from the dehiscent anthers until they are disturbed by fig wasps. The female wasps open the anthers and collect pollen with their antennal scrapes, mandibles and legs, and then carry pollen to the female receptive syconia where fertilization takes place. Meanwhile, some of the female wasps lay eggs in the male receptive syconia. It takes about 3-67 min to search for the receptive syconia for pollination, and 15-23 h to enter the female receptive syconia. The number of female wasps entering a syconium has close relation with the impregnation and seed_bearing rate of female flowers, as well as the oviposition and reproduction rate of the fig wasps themselves. F. hispida is endowed with a relatively high level of seed bearing (54.1%-82.5%, average 73.8 %). The wasp oviposition rate on the male flowers is between 72.3% and 93.8% with a mean of 84.4%.

Determination of toxic elements, essential elements, pesticide residue and aflatoxins ^{(28, 29, 30, 31, 32)}

An attempt has been made to evaluate the ficus species Ficus hispida for HPTlC Finger print profile. The toxic elements such as lead, cadmium, mercury and arsenic and also the essential minerals like calcium, iron, copper, manganese, zinc, nickel and cobalt and chromium analysis were carried out using Atomic Absorption Spectroscopy. Pesticide residue and aflatoxins were also carried out using GC-MS and HPLC respectively. The study revealed that heavy metals are within the permissible limits. Pesticide residue and aflatoxins were absent in the fruit of Ficus hispida. The HPTLC Finger print of Ficus hispida showed 13 peaks in the in the solvent system toluene: ethyl acetate: formic acid (9:1:0.1).

Traditional uses of Ficus hispida ⁽²⁵⁾

In Ayurveda system:

In Ayurveda it is been commonly known as Kaakodumbra, Phalgu, Malapu. In case of Leukoderma the hot decoction of roots are given internally and medicinal plaster externally as per prescribed by the Charka and Shushruta. The roots are pounded with rice water is been prescribed for checking intrinsic haemorrhage and its formulation is called as Raaj maarttanda. The fruit of kaakodumbra and honey are used in leucoderma and the formulation name is Vrindamaddhava. The tender leaves are cooked with the cow’s milk and Piper longum and it is been used in the case of cough and asthama and its formulation is known as Vaidya Manoramaa. Its juice is been used in ear-ache. It is also been used in a form of oil which is known as Chitrakadi Taila. (refer. Comparative std 3,6)

In Unani system:

In Unani system of medicine, Ficus hispida is known as Anjir Drishti. Its roots and bark are been used as blood purifier and drastic purgative. The anti-inflammatory formulation named Zimad-e-Kibreet of Anjir Drishti is applied externally in induration of spleen. The latex of the plant is used in ringworm. The paste of ripe fruits is used for goitre.

Pharmacological activities:

In Alzheimer’s disease⁽³³⁾

Alzheimer’s disease is a primary degenerative disease of the central nervous system. The progression of Alzheimer’s disease will ultimately lead to dementia, behavioral and cognitive impairments. The study was designed to determine the ameliorating effect of ethanolic leaf extract of Ficus hispida Linn. (EEFH) on (amyloid beta) Aβ 25-35-induced cognitive deficits and oxidative stress in mice. Animals were treated with EEFH for periods of 4 weeks dose-dependently (200 and 400 mg kg-1) then received a single intracerebroventricular (i.c.v.) injection of Aβ 25-35 (10 μg mouse^-1). Behavioural changes in the mice were evaluated using passive avoidance, Y-maze, hole board and water-maze tests.

Anti-diarrhoeal activity ⁽⁴⁾

Methanol extract of F. hispida L. showed significant inhibitory activity against castor oil-induced diarrhoea and PGE2-induced enter pooling in rats. It also showed a significant reduction in gastro-intestinal motility on charcoal meal test in rats. The results obtained establish the F. hispi da leaf extract as an anti-diarrhoeal agent.

Anti-Hyperlipidemic Activity ⁽³⁵⁾

Anti-hyperlipidemic activity of the methanolic plant extract of Ficus hispida Linn .f. leaves was evaluated against elevated cholesterol, triglycerides level in Triton – WR 1339 (Tyloxapol) induced hyperlipidemic mice model. Administration of the leaf extract of Ficus hispida at doses of 125, 250, and 500 mg/kg respectively, showed a significant reduction in serum lipid parameters such as Total Cholesterol, Triglycerides, VLDL and LDL level as compared to the Tyloxapol treated control group, indicating that the leaf extract of Ficus hispida possessed Antihyperlipidemic properties.

Cardio-Protective Activity ⁽¹²⁾

The methanolic extract of leaf of Ficus hispida was revealed to have cardioprotective activity. The extract of 400mg\kg of body weight was administered orally for 10 days. The cardiac oxidative stress injury was induced by Cyclophosphoamide to rat heart and its dose was 200mg\kg body weight. This showed that the extract exhibited a significant inhibition of lipid peroxidation and increased the level of superoxide dismuthase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase and reduced the glutathione activity in heart tissue provoked by cyclophosphamide.

Anti-Oxidation Activity ⁽³⁵⁾

The methanolic extract of leaf of Ficus hispida was evaluated to have anti-oxidation activity. The effective dose was found to be 400mg/kg of the body weight and the treatment was given for 21 days. The inducing agent was used Azathioprine which caused liver injury in the male Wister rats and its inducing dose was 50mg/kg of the body weight. Invitro estimation of the effect of the drug was done by checking enzymes like 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide. The in vivo activity, the use Azathioprine caused liver injury which resulted in the drop of the various enzymes, but with treatment of the extract of Ficus hispida caused anti-oxidant status normally.

Oxidative Anti-inflammatory Activity ⁽¹³⁾

Diabetes mellitus is a metabolic disorder characterized by persistent hyperglycemia, and insufficiency of insulin secretion and/or insulin resistance. Mounting evidence in both experimental and clinical studies suggests that oxidative stress plays a key role in the pathogenesis of diabetes mellitus and its complications. The objective of the present study was to investigate the effect of methanolic leaf extract of Ficus hispida on antioxidants, lipid peroxidation and inflammatory markers like tumor necrosis factor-alpha (TNF-α) activity in the brain of diabetic encephalopathy (DE) rats. DE rats displayed declined levels of endogenous antioxidants [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)], as well as elevated levels of malondialdehyde (MDA), nitric oxide (NO) and TNF-α. However, treatment with Ficus hispida significantly precluded these alterations in the DE rats, demonstrating that Ficus hispida can alter the oxidant stress and consequently improve the brain homeostasis.

Anti-Convulsant and Sedative Activity ⁽¹¹⁾

The central nervous system (CNS) depressant and anticonvulsant activities of the methanol leaf extract of Ficus hispida Linn were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behaviour for sedation tests, and strychnine, picrotoxin, and pentylenetetrazole-induced convulsions in mice. Ficus hispida (200 and 400mg/kg, p.o.), like chlorpromazine HCl (1mg/kg,i.m.), produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behaviour. Ficus Hispida (200 and 400mg/kg) produced dose-dependent and significant (P < 0.05) increases in onset to clonic and tonic convulsions, and at 400mg/kg, showed complete protection against seizures induced by strychnine and picrotoxin but not with pentylenetetrazole. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity. These results suggest that potencially antiepileptic compounds are present in leaf extract of Ficus Hispida that deserves the study of their identity and mechanism of action.

Hepatoprotective Activity ⁽⁵⁾

The hepatoprotective effect of 50% ethanolic extract of Ficus hispida L (Moraceae) by carbon tetrachloride (CCl4) induced liver damage in rats. The 50% ethanolic extract of Ficus hispida was studied for their hepatoprotective effects on CCl4 induced liver damage on Wistar albino rats. The degree of protection was measured by physical changes (liver weight), biochemical (SGPT, SGOT, ALP, total bilirubin, albumin and decreases in total protein). Pretreatment with extract significantly prevented the physical, biochemical changes induced by CCl4 in the liver. The effects of extract of Ficus hispida were comparable to that of standard drug, Silymarin. These results indicated that the Ficus hispida could be useful in preventing chemically induced acute liver injury. The present study, it can be concluded that, the 50% ethanol extracts of Ficus hispida possesses significant hepatoprotective activity.

Anti-Neoplastic activity ⁽³⁶⁾

Stems of Ficus hispida L. have long been prescribed as one of the constituents in various Thai traditional remedies for cancer therapy. In the present study, crude ethanol extract and its sequential fractions from Ficus hispida L.: water, methanol: water, methanol and ethyl acetate fraction were tested invitro against SKBR3, MDA-MB435, MCF7 and T47D human breast cancer cell lines. The results have shown that the methanol extract exhibited antineoplastic activity against T47D cells. The cytotoxic activity was further examined by MTT assay with more dilution, colony forming assay and cell cycle analysis. The IC50 of this extract against T47D cell was 110.3 +/-9.63 g/mL by MTT assay and colony forming assay confirmed the cell growth inhibition in a dose-dependent manner. Cell cycle analysis demonstrated a rising of apoptotic cell population in herbal treated cells. Therefore, F. hispida L. Used in traditional medicine may provide some benefits in the treatment of breast cancer.

Anti-Ulcer activity ⁽¹⁵⁾

The methanolic extract of Ficus Hispida at doses 200 and 400 mg/kg was found to be effective by 63.8 and68.44% respectively in aspirin (ASP) induced ulcer model and significantly reduced free and total acidity. It was observed that anti-ulcer effect of Ficus Hispida might be due to its cytoprotective effect rather than antisecretory activity. Conclusively, Ficus Hispida was found to possess potent anti-ulcerogenic as well as ulcer healing properties and could act as a potent therapeutic agent against peptic ulcer disease.

Hypoglycaemic activity ⁽¹⁴⁾

Ghosh et al, have successfully demonstrated the hypoglycemic activity of Ficus Hispida bark in diabetic albino rats. They reported that water soluble portion of ethanolic extract of the bark showed significant reduction of blood glucose level, increase in the uptake of glucose and increase in the glycogen content of liver, skeletal muscle and cardiac muscle. They also revealed the interaction of the constituent of the extract with insulin on concomitant administration, but the compound involved is not yet established.

Wound-healing activity ⁽³⁷⁾

Ethanolic extract of roots of Ficus hispida was investigated in normal and dexamethasone depressed healing conditions, using incision, excision and dead space wound models in albino rats. The root extract of Ficus hispida has shown the maximum breaking strength compared to control group. The rate of epithelialization and wound contraction in excision model was better as compared to control groups. There was significant increase in granulation tissue weight and hydroxyproline content in dead space model compared to control group. The antihealing effect of dexamethasone was also reverted by the administration of ethanolic extract of Ficus hispida in all the wound models .The results indicated that the root extract of Ficus hispida has a significant wound healing activity and also promotes healing in dexamethasone depressed healing conditions.

CONCLUSION:

In a country like India, there are 400 different tribal and ethnic groups which are in population about 7.5%. This primitive, tribal and rural population have discovered solution for the treatment of disease from the natural sources around them. The reason for the use of such natural sources is that as there is still the infancy of the modern health care facility in these areas. Thus, in the recent years, ethnomedical studies have received much attention as they bring to light the numerous known and unknown medical virtues, especially of plant origin, which need studies on modern scientific lines like phytochemical investigation, pharmacological screening and human studies Ficus hispida possesses various important pharmacological activities as discussed in the present review. Additionally, it is imperative that more pre-clinical and clinical studies along with the establishment of better quality control methods should be conducted to elucidate the unexplored potential of this plant.

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Received on 13.03.2013

Modified on 25.03.2012

Accepted on 03.04.2013

Research Journal of Pharmacognosy and Phytochemistry. 5(3): May-June 2013, 149-154