BIOPHYTUM SENSITIVUM DC.: A REVIEW

BIOPHYTUM SENSITIVUM DC.: A REVIEW

Manisha ¹ and Suresh Kumar^*2

Department of Pharmacognosy and Phytochemistry ¹, SGT College of Pharmacy, SGT University, Gurugram - 122505, Haryana, India.

Department of Pharmaceutical Sciences and Drug Research ², Punjabi University, Patiala - 147002, Punjab, India.

ABSTRACT: Biophytum sensitivum DC. (Family - Oxalidaceae), commonly known as “Lajjalu” in Northern India, is an annual herb that grows at the foothills of the Himalayas. It is an indigenous medicine, used against “Madhumeha” (Diabetes mellitus) apart from being used as tonic, stimulant, and in the treatment of stomach ache, asthma, insomnia, convulsions, cramps, chest-complaints, inflammations, tumours and chronic skin diseases. It has been scientifically screened for various pharmacological activities such as anti-tumour, antipyretic, immunomodulatory, antidiabetic, antiulcer, radio-protective, larvicidal, antibacterial and antioxidant. Phytochemical investigations showed the presence of flavonoids and phenolic compounds as the major constituents. The present work attempts to compile a review on macroscopic characteristics, chemical constituents, pharmacological reports, clinical studies, formulations and patents listed for this plant. The data has been collected from major databases like Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, Scirus, Science Direct, and other online and electronic databases’ which has then been systematically collated for a holistic review about Biophytum sensitivum.

Biophytum sensitivum, Diabetes, Flavonoids, Oxalidaceae

INTRODUCTION: The nature has blessed us with numerous “gifts” in this world. The plants are one of them, which form the basis of life and give us not only food and shelter but also the medicine to alleviate ailments, relieve pain and for longevity. According to W.H.O. about 75-80% of the world population, mainly in the developing countries still use plant based medicines for primary health care.

Many of the currently available drugs were derived directly or indirectly from phytochemicals ¹. India has a rich heritage of usage of medicinal plants in the Ayurvedic, Siddha and Unani systems. The country has about 15000 medicinal plants that include 7000 plants used in Ayurveda, 700 in Unani, 600 in Siddha, 450 in Homeopathy and 30 in modern medicines ².

1. Biophytum Genus: Biophytum is a genus of about 50 species of annual and perennial herbaceous plants distributed in tropical Asia, Africa, America and Philippines. In India, nine species are found and out of these only three species viz., Biophytum sensitivum DC. (Syn Biophytum petersianum Klotzsch.), B. reinwardtii Edgew. and B. umbraculum Welw. are reported to have ethnomedicinal properties ³. B. sensitivum (Family - Oxalidaceae) commonly known as ‘Nagbeli’ and “Lajjalu”, is an annual herb that grows at the foothills of the Himalayas, around the inner Tarai region (east of Koshi river) in Eastern Nepal ⁴.

2. Traditional Uses of Biophytum sensitivum: In Ayurveda, it is a tonic, stimulant and used in the treatment of stomach ache, diabetes and asthma. It is also used in insomnia, convulsions, cramps, chest-complaints, inflammations, tumours, chronic skin diseases. Pounded plants are given in insomnia ⁵. The decoction of the root is given in fever, gonorrhoea and lithiasis. The leaves are diuretic, astringent and antiseptic. Decoction of leaves is used as an expectorant and is given in asthma and phthisis. Paste of the leaf is applied to wounds and cuts to stop bleeding. The powdered seeds are applied to wounds, and (with butter) to abscesses to promote suppuration ⁶. The crushed whole plant is used in chronic skin troubles. It is eaten to induce sterility in man. It is a folk medicine against “Madhumeha” (Diabetes mellitus), particularly in Eastern Nepal ^{7, 8}. In Siddha system, the grounded leaves are given along with butter milk for diarrhea, grounded seeds are applied over wound and ulcer, the samoolam of this plant is mixed with honey and given for cough and chest congestion, and paste of the leaves is applied over burns and contusions ⁹. B. sensitivum is one of the plants used against snake envenomation. The whole part of plant is used to counteract the snake venom activity ¹⁰. It is one of the auspicious herbs that constitute the group “Dasapushpam”, which comprise ten potential herbs which are culturally and medicinally significant to the people of Kerala in India ¹¹. During the last few decades, extensive research has been carried out to elucidate the chemistry, biological activities, and medicinal applications of B. sensitivum, it has been proved to be revolutionary therapeutic plant to combat life threatening diseases.

3. Distribution and Propagation: It is a common weed distributed in wet lands (mostly plains) of tropical Africa, Asia and India, and is found normally in the shade of trees and shrubs, in grasslands, at low and medium altitudes. It is commonly known as by various vernacular names such as Lajjalu (Hindi), Sensitive Plant (English), Mukkutti (Malayalam), Alambusha, Jalapushpa, Panktipatra, Pitapushpa (Sanskrit), Nilaccurunki, Tintanali (Tamil), Jhalai (Bengali), Hara Muni Jalapushp (Kannada), Jharera, Lajwanti (Marathi), Attapatti, Chumi, Jala (Telugu) and Alleluya (French) ¹². It is easily propagated through seeds. Seeds are propelled away from the plant by built up tension from when they dry and sown in a mixture of moist peat and sand, after sowing it is covered with a transparent cover to increase humidity. It requires bright indirect sunlight to partial shade, medium humidity and 16 °C to 29 °C temperature, moist soil and water soluble fertilizers during growth season ¹³.

4. Morphological Description of the Plant: It is an annual herb which looks like a miniature palm, with unbranched, erect, glabrous or hairy stems from 2.5 to 25cm.

4.1. Leaves: Leaves are green in color, peripinnate, 3.7-12.7cm long, crowded into a rosette on the top of the stem; leaflets 6-15 pairs, oblong, very variable in size, 6-12 mm long ^{5, 13}. The remarkable feature of leaflets is their ability to fold together representing an extreme form of “sleep movement” which is exhibited by a lot of members in this family. When applying pressure, tapping or damaging them they fold together in a few seconds. This plant also displays this behavior when the light drops at night. This ability is not restricted to the leaves; the peduncle which carries the flowers has the same ability and also drops at night ¹⁴.

4.2. Flowers: Flowers are dimorphic, normally yellow, white or orange with a red / orange streak in the center of each of the 5 petals on long peduncles of various lengths; petals usually twice as long as the sepals, capsules elliptic, shining ^{13, 15}. The flowers are many, and crowded at the apices of the numerous peduncles. The sepals are subulate-lanceolate, striate, and about 7 millimeters long.  Interesting feature of flowers of this plant is heterostyly. Heterostyly in B. sensitivum is responsible for 3 flower morphs. The three morphs (tristylous) each have a stable difference in pistil- and stamen length. The fruit is a capsule which is ellipsoid, apiculate, slightly exceeding the sepals. Seeds are ovoid and transversely striate ¹⁴.

5. Regeneration of Biophytum sensitivum: B. sensitivum has been studied for the potential of regeneration by callus culture and micro-propagation techniques ¹⁶. Microprapagation of leaf and shoot tip explants in MS medium containing 0.05mg l-1 TDZ and 1mg l-1 BAP results in formation of 14 shoots. The in vitro regenerated plants from the callus obtained from shoot tip and leaf explants were hardened, transferred to the field, established well and found normal. It is reported the regeneration of the plant through direct and indirect organogenesis and somatic embryogenesis using MS medium supplemented with 2, 4-D or NAA in combination with BAP induced callusing in stem, inflorescence tip and flower bud explants. Eighty percent of the root plantlets and ninety percent of the somatic embryo derived plantlets survived on soil medium ¹⁷.

6. Chemical Constituents: The whole plant contains various chemical constituents like phenolic and polyphenolic compounds, saponin, essential oil, polysaccharides and pectin. The main constituent was found to be amentoflavone. Amentoflavone was quantified by reversed phase high performance liquid chromatography (RP-HPLC) in methanolic extract of roots, stems and leaves and the contents were estimated to be 0.26% in roots, 0.33% in stems, and 0.012% in leaves ¹⁸. High-performance thin layer chromatographic (HPTLC) method has been developed for estimation of amentoflavone and was validated for precision (intra- and inter-day), repeatability, and accuracy were 0.52-1.36% ¹⁹. Various chemical constituents of B. sensitivum have been summarized in Table 1.

TABLE 1: REPORTS ON ISOLATED PHYTOCONSTITUENTS FROM B. SENSITIVUM

Amentoflavone                   Cupressuflavone            Orientin              Isoorientin

Isovitexin                                     (-)- epicatechin                        Luteolin-7-methyl ether

Luteolin-7-o-glucoside          4-caffeoylquinic acid   1, 2-dimethoxy benzene    5-caffeoylquinic acid

1,4-dimethoxy benzene     2-methoxy-4-methyl phenol         Isophorone

 Linalyl acetate          1-octen-3-ol                        Linalool oxide

FIG. 1: CHEMICAL STRUCTURES OF IMPORTANT CONSTITUENTS OF BIOPHYTUM SENSITIVUM

7. Pharmacological Reports: The plant has been screened for a number of pharmacological activities. It has been reported to exhibit anti-tumor, antipyretic, immunomodulatory, anti-diabetic, antiulcer, radioprotective, larvicidal and antioxidant activities. Reported pharmacological activities of B. sensitivum have been summarized in Table 2.

TABLE 2: PHARMACOLOGICAL ACTIVITIES OF BIOPHYTUM SENSITIVUM

PE, CE, ME and WE represents Petroleum ether, Chroloform, Methanol and Water extract.

B. subtilis, S. aureus, Strep.pneumonia, K.pneumoniae, Salm. typhi, P. vulgaris, and E. coli, A. fumigatus, A. niger and C. neoformans represents Bacillus subtilis, Staphylococcus aureus, Streptococcus pneumonia, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Escherichia coli,  Aspergillus fumigatus, Aspergillus niger and  Candida neoformans respectively.

8. Toxicity Studies: Acute toxicity of B. sensitivum extracts was studied in rodents. The aqueous extract of leaves of the plant was studied and found non-toxic at the dose levels of 100, 200 and 300 mg/kg body weight by oral route in mice ²⁷. The methanolic extract of the B. sensitivum whole plant is well tolerated up to an oral dose of 4000 mg/kg of body weight as no mortality was observed within a period of 24 h ⁴⁹. The median lethal dose (LD₅₀) of the hexane, chloroform, ethyl acetate, n-butanol and ethanol extracts of the plant were found to be greater than 1g/kg when administered by intraperitoneal route to rats ⁵⁴.

9. Clinical Studies: Biophytum sensitivum is used in the treatment of diabetes in the Ayurvedic system of medicines. Traditionally it is said to have a insulin like compound. The mechanism of action is not well understood but appears to have insulin-tropic properties. Clinical studies have been reported on the formulation containing B. sensitivum ⁶⁰. DB14201 has been marketed since 2002 under Ayurvedic license issued by Drug Controller of the State of Kerala, under the trade name Diabedrink. It is a combination of 16 herbs used in Ayurveda.

It contains Zizyphus jujube, Terminalia chebula, Mangifera indica, Emblicao-fficinalis, Embelia ribes, Curcuma longa, Aerva lanata, Syzygium cumini, Coscinium fenestratum, Salacia Oblonga, Cyclea peltata, Biophytum sensitivum, Strychnos potatorum, Cyperus rotundus, Vetiveria zizanioides, and Centella asiatica as ingredients. Subject blinded, placebo controlled, randomized clinical studies have been repoted on 30 patients suffering from Type 2 Diabetes in the ages of 29-71 of both gender which were on single oral hypoglycemic agent Glibenclamide, since more than three months but with inadequately controlled blood sugar levels (FBS level >120 mg/dl and/ or PPBS levels >200 mg/dl) on the day of recruitment.

The study period for each subject was 90 days with a follow-up of 15 days thereafter. The entire evaluation was completed in 11 months. It is reported that the herbal formulation DB14201 is safe in T2DM patients when administered along with glibenclamide and improves the effectiveness of glibenclamide in offering better glycemic control. It also provides significant improvement in fasting and post prandial blood sugar levels in comparison to addition of placebo and also significantly reduces HbA1c levels.

10. Formuations of Biophytum sensitivum: Herbal creams and gels were prepared by incorporating the dry methanolic extract of whole plant of B. sensitivum into emulsifying cream and aqueous washable gel base. It was evaluated for in vitro antibacterial efficacy against four different bacterial strains (Salmonella typhi, Staphylococcus aureus, Escherichia coli and Bacillus subtillis) using the agar well diffusion method. The results showed that B. sensitivum has high potential as antibacterial agent when formulated as cream and gel for topical use ⁶¹. An optimized tablet formulation was prepared of B. sensitivum using the dried whole plant methanolic extract.

It was evaluated for their antioxidative properties in vitro based on their total flavonoid content (TFC) against a standard flavonoid, Quercetin and also in vivo for antidiabetic activity in Streptozotocin (STZ) induced diabetic rats against Glibenclimide, an antidiabetic drug. The drug exhibited antioxidant and antidiabetic properties of the formulation ⁶².

11. Patent Related to Biophytum sensitivum: Herbal formulation comprising of extracts from selected Indian medicinal plants Zizyphus jujube, Terminalia chebula, Mangifera indica, Emblicao-fficinalis, Embelia ribes, Curcuma longa, Aerva lanata, Syzygium cumini, Coscinium fenestratum, Salacia Oblonga, Cyclea peltata, Biophytum sensitivum, Strychnos potatorum, Cyperus rotundus, Vetiveria zizanioides, and Centella asiatica as ingredients used for prevention and treatment of diabetes and associated complications has been patented ⁶³.

CONCLUSION: Traditionally the parts of the plant have been known to possess a wide spectrum of medicinal properties namely antiseptic properties, including positive effects in variety of skin infections and in the treatment of diabetes. Antibacterial, antifungal and antidiabetic activities have been proved by the scientific research work. Biophytum sensitivum is widely prescribed for the treatment of diabetes in Ayurvedic system of Medicine. The whole plant is also used traditionally in the treatment of various ailments.

The plant has been evaluated exhaustively for various pharmacological activities and reported to possess anti-inflammatory, antipyretic, antimicrobial, antiobesity, antioxidant, anti-diabetic, anti-fungal, anti-cancer, larvicidal, anti-obesity, anti-hypertensive, antiepileptic, wound healing and antifertility activities.

No systematic work has been carried out to isolate bioactive constituents responsible for afore-mentioned bioactivities. The plant contains phytoconstituents like flavonoids, steroids, phenolic compounds but till now only nineteen phytoconstituents have been isolated. Amongst these constituents, only flavonoids (amentoflavone) have been suggested to possess most of pharmacological activities. These observations suggest that detailed investigations are needed with a view to isolate bioactive constituents, and to standardize the plant on the basis of isolated bioactive markers. Only one formulation containing B. sensitivum as one of the ingredients has been patented which is used in the treatment of diabetes and diabetic complications. It has been found to be safe in a toxicity studies.

Clinical studies on 30 type 2 diabetic patients have been conducted to observe antidiabetic potential of the plant showed beneficial effects in diabetic patients. Finally, it is concluded that B. sensitivum is the source of plenty of bioactive constituents which has the potential to be developed as efficacious and safer drugs.

ACKNOWLEDGEMENT: Authors are thankful to Hindu College of Pharmacy, Sonipat, for providing necessary facilities during the work.

CONFLICT OF INTEREST: The authors declare no conflict of Interest.

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    Manisha and Kumar S: Biophytum sensitivum DC.: A Review. Int J Pharm Sci Res 2018; 9(1):27-36.doi: 10.13040/IJPSR.0975-8232. 9(1).27-36.

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