Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67

International Journal of Current Research

and Academic Review ISSN: 2347-3215 Volume 4 Number 7 (July-2016) pp. 57-67 Journal home page: http://www.ijcrar.com doi: http://dx.doi.org/10.20546/ijcrar.2016.40 7.008

Biophytum sensitivum Chemical Constituents and Medicinal Properties: A Review

Mathew George, Lincy Joesph and Umesh Kumar*

Pushpagiri College of Pharmacy, Tiruvalla, Kerala-689107

*Corresponding author KEYWORDS ABSTRACT

Biophytum World is rich in knowledge with a wide diversity of medicinal which sensitivum, provide people with traditional healing methods for diseases in general phytochemical, healthcare area. is a with various medicinal phytocontituents. properties such as analgesic, anti-pyretic, anti-inflammatory, immunomodulatory, antitumor, antidiabetic, antioxidant, antibacterial, antihypertensive, chemoprotective, radioprotective, antifertility and anti- asthmatic. This review study provides an extensive detail about the phytochemical, pharmacological and folkloric uses of Biophytum sensitivum. It has been used indigenously in the field of Ayurvaeda, Sidhha and Unani for

many decades. Various parts of the plant has the presence of variety of phytoconstituents such as flavonoids, saponins, tannins, terpenes, steroids, amino acids, essential oil, polysaccharides and pectin.

Introduction

The genus Biophytum is a member of the distributed up to an altitude of 1,800 m and family and distributed in is available during the rainy season in moist tropical Asia, Africa, America and the shady places (Warrier et al., 2014). The plant Philippines. In , nine species of is traditionally used for centuries in the Biophytum are prominently found and out of treatment of various health aliments. It is an these, three species viz. Biophytum important medicinal plant in the Indian sensitivum DC. Syn. Oxalis sensitivum traditional system of medicine like Linn., Biophytum reinwardtii Edgew and Ayurveda (The wealth of India, 1988). It is Biophytum umbraculum Welw. Syn. extensively used for its wide therapeutic Biophytum petersianum Klotzsch are potential such as analgesic, anti-pyretic, reported to have ethnomedicinal potential. anti-inflammatory, immunomodulatory, Biophytum sensitivum (L.) DC (B. antitumor, antidiabetic, antioxidant, sensitivum), commonly known as ‘Life antibacterial, antihypertensive, chemo- plant’, is a mesophytic under-shrub growing protective, radioprotective, antifertility and in slightly moist places. The plant is anti-asthmatic.

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 Description

It is a small plant, rarely exceeds 2.5-20 cm in height and form an unbranched woody erect stem. All leaves grow on the top of the stem. Leaves are abruptly pinnate, sensitive, 3.8-12.7 cm long and are made of 8-17 pairs of leaflets. Leaflets are opposite, 1 cm long, terminal pairs the largest and pairs becoming smaller downwards. Flowers are dimorphic, 8 mm across, yellow and crowded at apices of the peducles. The sepals are lanceolate, 7 mm long with parallel nerves. Corolla is much exceeding the sepals. Lobes are rounded and spreading. Style is nearly glabrous. Fruits are ellipsoid capsule. Seeds Different parts of Biophytum sensitivum are prominently ridges and transversely striated. The plant has been observed Taxonomical classification (Pullaiah, flowering and fruiting in the month of 2006) September to December (CSIR, 2004; Pullaiah, 2006). Kingdom: Plantae Phylum: Tracheophyta Class: Magnoliposida Order: Family: Oxalidaceae Genus: Biophytum Species: sensitivum Botanical name:Biophytum sensitivum (L.) DC

Vernacular names (Editorial Committee of the Flora of Taiwan, 1993) Flower of Biophytum sensitivum Common name: Life plant, little tree plant, sensitive plant French: alleluia Bengali:Jhalai Hindi:Lajalu, Lajjaalu, Lakshmana, Zarer Indo-China:Chua me Kannada:Haramuni, Jalapushpa Malayalam:Mukkutti Marathi:Jharera, Lajwanti, Lahanmulaka Sanskrit:Jhullipuspa, Lajjaluka, Panktipatra, Pitapushpa, Vipareetalajjaalu Tamil:Nilaccurunki, Tintaanaalee Telugu:Attapatti, Chumi, Jala pupa Whole plant of Biophytum sensitivum

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 Physiochemical analysis (Kumaratunga, was transferred to the original crucible and 2003) ignited for 15 min. at a temperature not exceeding 450 °C. Water soluble ash is the Extractable Matter calculated difference in weight between the total ash and the residue remaining after Crushed, air dried plant material (about 4 g) treatment of the total ash with water. was weighed to a glass-stoppered conical Moisture content of the samples was flask. Solvent (100 mL) was added, estimated and all the calculations were done weighed, shaken well and allowed to stand on dry weight basis. for lh. It was then boiled for 1 h and cooled. The weight was readjusted with specified Phytochemistry (Abinash et al., 2012) solvent and filtered Filtrate (25 mL) was taken, solvent was evaporated and oven Phytochemical studies of B. dried at 105 °C for 6 h, cooled in a sensitivum showed that it contains a number desiccator and weighed. of phenolic and polyphenolic compounds, saponin, essential oil, polysaccharides and Total Ash pectin. The main bioactive constituents found are bioflavonoid, amentoflavone with Crushed, air dried plant material (about 4 g) minute amount of cupressoflavone. was weighed to a previously ignited crucible. The material was ignited by Other than amentoflavone, the flavonols gradually increasing the temperature to present were luteolin 7-methyl ether, 550°C until it was free from carbon. The isoorientin, 3’-methoxyluteolin 7-O- crucible was cooled and weighed glucoside, as well as two acids, 4- caffeoylquinic acid and 5-caffeoylquinic Acid Insoluble Ash acid, that were isolated from aerial parts of B. sensitivum. Further isolation and Hydrochloric acid (25 mL, cone. -70 g/L) quantification of C-glycosyl flavones and was added to the crucible containing total proanthocynidin from the plant showed the ash, covered with a watch glass and boiled presence of isoorientin, orientin, isovitexin, gently for 5min. The insoluble matter was isoorientin 7-O-glucoside, isoorientin 2”-O- collected on an ashless filter paper and rhamnoside in methanolic extract of the washed with hot water until the filtrate was leaves. From the roots, (–)-epicatechin and neutral. The filterp aper containing the epicatechin-(4β-8)-epicatechin insoluble matter was transferred to the (proanthocynidin B2) were isolated and the original crucible and ignited to a constant highest amount of C-glycosyl flavones was weight. found in leaves. The essential oil of air- dried B. sensitivum was investigated by gas Water Soluble Ash chromatography-spectroscopy (GC-FID and GC-MS) and was found to contain mainly Water (25 mL) was added to the crucible 1,4-dimethoxy benzene (24.9%), 1,2- containing total ash, covered with a watch dimethoxy benzene (10.6%) and 2-methoxy- glass and boiled gently for 5min. The 4-methyl phenol (3.5%), the monoterpenes insoluble matter was collected on an ashless (Z)-linalool oxide (8.1%) , (E)-linalool filter paper and washed with hot water. The oxide (5.2%), linalyl acetate (3.4%) , 1- filter paper containing the insoluble matter octen-3-ol (9.5%), isophorone (3.1%), and

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 69 minor compounds. The water extract of The analgesic activity of methanolic extract aerial parts contains a bioactive of Biophytum sensitivum showed analgesic polysaccharide, BP100 III, major part of effect by Tail flick method at the doses of which is composed of galacturonic acid and 100 and 200 mg/kg in mice. The analgesic rhamnose, with branches being present on activity in respective doses was found to be both the rhamnose and galacturonic acid 54.93% and 67.91% against acetic acid residues. induced writhing in mice.

Medicinal Uses It was concluded that methanolic extract The study revealed the insulinotropic effect showed significant increase in activity at of Biophytum sensitivum. The anti- higher dose. The anti-pyretic activity of inflammatory activity of aqueous and methanolic extract of Biophytum sensitivum methanol extracts of aerial parts and roots was tested against yeast induced pyrexia in were studied in the carrageenin-induced rat rats. The results showed that the rats treated paw oedema model. All the extracts except with plant extract at the dose of 100 and 200 the methanol extracts of aerial parts mg/kg showed significant decrease in body exhibited anti-inflammatory activity. Apart temperature and also this decrease is dose from this, mostly in ayurveda, this is a tonic, dependent. stimulant and in the treatment of stomach ache, diabetes and asthma. It is also used in Anti-inflammatory activity insomnia, convulsions, cramps, chest- complaints, inflammations, tumors, chronic The methanolic extract of whole plant of B. skin diseases. sensitivum was reported to have significant anti-inflammatory activity at the dose of 100 Uses as folklore medicine (Council of and 200 mg/kg in the carrageenin-induced, Scientific and Industrial Research, 1988; histamine-induced and dextran-induced paw CSIR, 2004; Kirtikar et al., 2005) oedema model in the rats (Jachak et al., The whole plant is dried, powdered and 1999). Anti-inflammatory activity of given internally to cattle to stop excessive aqueous extracts of aerial parts and roots, salivation. In the Philippines, the powdered methanol extract of aerial parts and seeds are used as vulnerary and along with ultrafiltration fractions of a methanol extract butter they are applied to abscesses to of roots of B. sensitivum were also evaluated promote suppuration. The crushed whole in the carrageenin-induced rat paw edema. plant is used in chronic skin troubles and is All the fractions except the methanol extract also eaten to induce sterility in man. A of aerial parts inhibited the formation of decoction of the leaves is given in asthma carrageenin-induced paw edema (Sekhar et and phthisis. The plant is also used in chest al., 2012). complaints, insomnia and convulsious cramps and inflammatory tumors. The plant Amentoflavone and procyanidines isolated decoction is used in amenorrhea and from the B. sensitivum has been reported to dysmenorrhea and its powder for the possess in vivo anti-inflammatory activity gonorrheal infection and lithiasis. and to inhibit COX when tested in vitro. Amentoflavone has been reported to Activity studies downregulates COX-2 expression with

Analgesic activity and Anti-pyretic concomitant inhibition of NF-κB/DNA activity (Chatterjee et al., 2008) binding activity with inhibition of

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 degradation of IκBα and NF-κB Methanolic extract of B. sensitivum have translocation into the nucleus in TNFα- reported to produce apoptotic effect by activated A549 cells (Guruvayoorappan et regulating bcl-2, Caspase-3 and p53 genes in al., 2007). B16F-10 cells and regulates nitric oxide and proinflammatory cytokine production in Immunomodulatory activity B16F-10 cells, TAMs and peritoneal macrophages. Amentoflavone isolated from The methanolic extract of B. sensitivum the B. sensitivum found to augments increased the total WBC count and number lymphocyte proliferation, natural killer cell of bone marrow cells. It is concluded that B. and antibody dependant cellular cytotoxicity sensitivum has stimulatory effect on through enhanced production of IL-2 and haematopoetic system, differentiation of IFN-gamma and restrained serum sialic acid stem cells and humoral arm of immune and gamma glutamyl transpeptidase system. It is also found that the methanolic production in Ehrlich ascites carcinoma cells extract of B. sensitivum stimulates the bearing mice. immune cell system in Ehrlich ascites tumor bearing BALB/c mice, leading to The aqueous extract of B. sensitivum leaves potentiation of immune cell proliferation also found to inhibit the tumor volume, and NK cell mediated tumor lysis viable cell count and enhancement of (Inngjerdingen et al., 2008). The pectic survival time of DLA bearing mice. It is polysaccharide (BP1002) obtained from a concluded that aqueous extract of B. hot water extract of the aerial parts of B. sensitivum leaves has significant anti-tumor sensitivum is reported to have ability to activity. activate macrophages and dendrite cells (Gronhaug et al., 2011). The pectin Antiangiogenic activity polysaccharide (BPII) from the aerial parts (Guruvayoorappan et al., 2007) of B. sensitivum and its fragments (BPII.1 and BPII.2) expressed immunomodulating Amentoflavone isolated from B. sensitivum activity against Peyer’s patch immune reported to inhibit tumor directed competent cells and macrophages angiogenesis by disrupting the integrity of (Guruvayoorappan et al., 2008). endothelial cells and by altering the endogenous factors such as IL-1β, IL-6, Antitumor activity (Guruvayoorappan et TNF-α, GM-CSF and VEGF that are al., 2007; Inngjerdingen et al., 2008; required for the process of Gronhaug et al., 2007) neovascularization. This antiangiogenic activity of amentoflavone is responsible for The methanolic extract of B. sensitivum inhibition of tumor growth and metastasis. found to inhibit the growth of solid tumor induced by Dalton’s lymphoma ascites Antimetastatic activity (DLA) cells and ascites tumor induced by Ehrlich ascites carcinoma (EAC) cells. The Amentoflavone isolated from B. sensitivum extract was 100% toxic at a concentration of reduced experimental tumor metastasis at 0.5 mg/ml to both DLA and EAC cells. It the dose of 50 mg/kg for 10 consecutive was also found to be cytotoxic towards L929 days in C57BL/6 mice injected with B16F- cells in culture at a concentration of 0.1 10 melanoma cells (Guruvayoorappan et al., mg/ml. 2008).

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 Amentoflavone found to produce Anti-bacterial activity (Natarajan et al., antimetastatic effect by altering 2010) proinflammatory cytokine production and inhibiting the activation and nuclear The methanol, chloroform, acetone and translocation of p6, p50, c-Rel subunits of petroleum ether extracts of leaves of B. nuclear factor-kappaB, and other sensitivum showed antibacterial activity transcription factors such as c-fos, activated against B. subtillis, S. aureus, S. pneumonia, transcription factor-2, and cyclic adenosine K. pneumonia, S. typhi, P. vulgaris and E. monophosphate response element binding coli by agar well diffusion method in the protein in B16F-10 melanoma cells range of 7-25 mm. The acetone extracts (Guruvayoorappan et al., 2008). showed remarkable anti-bacterial activity against B. subtillis. The extracts from the Hypoglycaemic activity (Puri et al., 1998; leaves exhibited considerable and variable Puri et al., 2001; Puri et al., 2008; Ananda inhibitory effects against most of the tested et al., 2012) microorganism.

The aqueous solution of B. sensitivum leaf Antioxidant activity (Guruvayoorappan et extract was administered to rabbits at the al., 2006) dose of 200 mg/kg to study its effect on alloxan-induced diabetes. There was B. sensitivum extract was found to scavenge significant improvement in the glycaemic superoxide radicals, hydroxyl radicals and state in the subdiabetic and mild diabetic inhibited in vitro lipid peroxidation at rabbits only. The results indicated that the B. concentrations of 50, 95 and 20 μg/ml sensitivum has hypoglycaemic effect (IC50) respectively. The extract also mediated through pancreatic beta-cell scavenged nitric oxide (IC50 = 100 μg/ml). stimulating action. The mild hypoglycemic The extract found to induce the dose- activity of crude extract of B. sensitivum was dependent scavenging of nitric oxide in also demonstrated in the obese glucose- culture. intolerant rabbits at the dose of 200 mg/kg. Intraperitoneal administration of B. Effect of oral administration of aqueous sensitivum extract inhibited superoxide solution of B. sensitivum leaf extract at the generation in macrophages in vivo in mice. dose of 200 mg/kg for 28 days was studied The extract also produced significant in normal and streptozotocin-nicotinamide- increase in catalase activity, glutathione, induced diabetic rats. The B. sensitivum leaf glutathione-S-transferase and glutathione extract treatment significantly reduced the reductase. The levels of glutathione blood glucose and glycosylated peroxidase decreased after administration of haemoglobin levels and significantly B. sensitivum extract. These results indicate increased the total haemoglobin, plasma that B. sensitivum extract has significant insulin and liver glycogen levels in diabetic antioxidant activity both in vitro and in vivo. rats. It also increased the hexokinase activity and decreased glucose-6-phosphatase, Antihypertensive activity (Titrikou et al., fructose-1,6-bisphosphatase activities in 2007) diabetic rats. The results indicate that aqueous solution of B. sensitivum leaf The whole plant extract of B. sensitivum is extract possesses significant antidiabetic reported to possess antihypertensive activity.

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 potential on guinea pig and rat model. The protective activity against extract non-competitively antagonized cyclophosphamide induced toxicity + calcium chloride and high-K -induced (Guruvayoorappan et al., 2007). contraction of isolated rat aorta in a concentration-dependant manner. Radioprotective activity

The extract also found to inhibit Methanolic extract of B. sensitivum was noradrenaline-induced contractions of aorta. found to enhance immunity as well as These results strongly indicate that stimulate production of IL-1β, IFN-γ and antihypertensive effect of B. sensitivum GM-CSF at the dose of 50 mg/kg in mice results from inhibition of calcium influx via exposed to whole body gamma irradiation. It both voltage and receptor operated calcium is concluded that B. sensitivum extract provides protection against radiation- channels. induced hemopoietic damage Antifertility activity (Guruvayoorappan et al., 2008).

Ethanol, ethyl acetate, chloroform and n- Larvicidal activity butanol extracts of whole plant of B. sensitivum were studied for the antifertility Acetone extract of leaves of B. sensitivum potential at the dose of 400 mg/kg in female was found to be effective larvicidal, Wistar albino rats. All the extracts inhibited pupicidal and also interfered with the normal pregnancy with a significant reduction in development and emergence of adult number of implants as compared to control mosquitoes at the concentration of 10, 15 animals. The ethanolic extract exhibited and 25 mg/L on Aedes aegypti mosquito in a maximum (100%) antifertility activity. The dose dependant manner. It is concluded that activity was reversible on withdrawal of the B. sensitivum is having an excellent potential as Larvicidal agent against A. treatment of the extract. aegypti strain (Shivakumar et al., 2012). Chemoprotective activity Complement fixing activity Intraperitoneal administration of alcoholic extract of Biophytum sensitivum increased The aqueous extract of aerial part has the the total WBC count, bone marrow polysaccharide fraction, BP100 III, and has cellularity, alpha-esterase positive cells and a monosaccharide composition typical for weight of lymphoid organs in mice with pectic substances, that exhibits potent dose- cyclophosphamide induced toxicity. The dependent complement fixating activity. The extract treatment found to restore GSH in fractions of BP 100 III were prepared by the liver and intestinal mucosa, serum and liver endo-α-D-(1→4)-polygalacturonase ALP, GPT and lipid peroxidation. degradation. The highest molecular weight fraction is BP 100 III.1 which has more The B. sensitivum extract reduced the level potent activity in the complement test of the pro-inflammaory cytokine, TNF-α system than the native polymer which and increased the levels of cytokines IFN-γ, consists of galacturonic acid and rhamnose sugar having additional arabinogalactan type IL-2 and GM-CSF in cyclophosphamide treated mice. It was concluded that II in polymer (Inngjerdingen et al., 2006). Biophytum sensitivum has significant

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Int.J.Curr.Res.Aca.Rev.2016; 4(7): 57-67 Anti-fungal activity antifertility and anti-asthmatic. It possess potential to treat different ailments and still The acetone extract of leaves of B. needs to be explored for various sensitivum had significant antifungal pharmacological activity. The future aspects activity. The leaf extract of B. sensitivum of the plant can be anti asthmatic as it inhibited the growth of fungal pathogens A. contains many of the phytochemicals and fumigatus, A. niger, C. neoformans and work has not been performed yet. Norcardia sp. in disc method (Vijayan et al., 2010). References

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How to cite this article:

Mathew George, Lincy Joesph and Umesh Kumar. 2016. Biophytum sensitivum Chemical Constituents and Medicinal Properties: A Review. Int.J.Curr.Res.Aca.Rev.4(7): 57-67. doi: http://dx.doi.org/10.20546/ijcrar.2016.407.008

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