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MEDICINAL IMPORTANCE OF MOLLUGO VERTICILLATA (MOLLUGINACEAE): A REVIEW

Over the years, the world has become common to pandemic diseases in humans with lot of ailments and untreated infectious disorders. Most of the laboratories across the globe run in with under developed vaccines and drugs for many diseases for its procurement and prevention. But the bioavailability of the drug in the market is less reached due to high cost and etc. In the current situation, plant saps and its extracts are used to counteract with the pathogens based on the information in traditional medicine. Most of the phytochemical enriched herb, weed or plants available commonly are used for treatments of various diseases. One of the herbs found is Mollugo verticillata (commonly known as ‘green carpet weed’). It is commonly used in treating fever, aches and other various ailments and it shows promising activity in pharmacological properties due to the presence of phytoconstituents like terpenoids, saponins and flavonoids. Finally, the plant extract has enormous medicinal importance. This review is a collection of overall research work on Mollugo verticillata plant and their medicinal compounds present.


INTRODUCTION
Medicinal plants research is one and remains to be the best area of research in development of newer and effective drugs [1,2] . It has been reported that extracts of plant are common in ancient medicine and their contribution with respect to health benefit was estimated over 80% of the world's total population [3,4] . Bioactive compounds are byproducts of the plant species and are therefore regarded as an invaluable repository of unusual chemical compounds since these secondary metabolites are like chemical fingerprints of each plant species [5] . According to the history, plants used in ancient medicine are used to treat various diseases and are a rich source of antioxidants [6] . In most of the cases, the research has confirmed by discovering the hypothesis on mechanism and mode of action of the plants through use of traditional medicine. Importance of medicinal plants in development of drugs is well known and humans have used and been using them for treatment of different ailments from the ancient days. The search for new pharmacologically active agents from natural resources such as plants, microbes, animals have led to the discovery of newer drugs which are effective, potent and are used clinically [7] . A herbal weed belonging to the family of Molluginaceae is used in traditional medicine in many Indian villages due to its various beneficial effects [8] . In general, several species belonging to Mollugo genus include, M. cerviana (thread stem), M. pentaphylla (African), M. nudicaulis (naked stem), M. verticillata (green) and M. oppositifolia (slender).
Mollugo verticillata L. (Family: Molluginaceae) is an annual herb commonly grown in warm and wet regions of the American continent [9] . The chemistry of these medicinal plants is differentiated by the production of triterpenesaponins and flavonoid compounds [10] . Ferreira et al. (2003) reported that triterpenesaponins and flavonoids derivatives possess a significant effect on the immune system [11] . Earlier, the immunomodulatory activity of triterpenesaponins has been stated in previous report [12] . In all of the Mollugo species Cglycosylflavonoid compounds are present [13] .
Apart from M. verticillata, other species of Mollugo are reported with high therapeutic activity. Mollugo cerviana (thread stem carpet weed) is used to treat jaundice [14] , suppressor for stomach ache and vaginal discharge after child birth [15,16] and increases eyesight [17] where roots are used in treating rheumatism [18] .
Different extracts (polar to non-polar) show distinct biological activities based on diverse chemical compounds present in them when extracted. The current review is described based on the literature collected and organized as growth and habitat of the plant, morphology, chemical composition and the medicinal properties of Mollugo verticillata.

Mollugo Verticillata
Mollugo verticillata (Fig. 1) belongs to family of Molluginaceae is an annual herb with prostrate growth habitat [11] . It is a common weedy plant grown in disturbed areas like fields, gardens, road sides and parking lots [19] . The plant is native to tropical America [20] and forms a prostrate circular mat that climbs rapidly on nearby plants. This plant is also known to be edible. The leaves are narrowly, whorled with 3-8 at each node. The length is 4-25mm long, 0.5-3mm wide, smooth and possess an obovate or spatulate shape. Leaves are mostly light-green in color with a reddish tinge at late phonological stage [21] . It grows and sprawl across the soil due to its habitat of prostrate growth and forms mats [11] . The flowers are formed in clusters 2-5 blooming from July to September. Color of the flower is white or greenish white with tiny 5-15mm stalks. Flowers turn into fruit which is egg shaped and 1.5-4mm in length and the seeds are 0.5 m long and are red to rusty brown in color [22][23][24] . [25]

Chemical Composition
However, Flavonoid aglycones, such as quercetin and apigenin (Fig. 2) are the effective inhibitors of nitric oxide production [25] . Ferreira et al. (2003) reported that compounds like quercetin and other flavonoid glycoside and triterpenoid glycoside showed immunomodulatory effects in Bacillus Calmette Guerin (BCG) antigen and Mycobacterium tuberculosis whole antigen induced mice peritoneal cell cultures [11] . Antonio and Vivit (2017) stated that only few reports show their phytochemistry, and among Mollugo species, M. oppositifolia, M. pentaphylla and M. nudicaulis had similar phytochemicals as M. verticillata [26] . The plant M. pentaphylla is reported to contain flavonoid compounds such as apigenin, mollupentin, mollugogenol A, B and D, along with triterpenoid, oleanolic acid and β-sitosterol [27] .

Traditional Uses
The ethnomedicinal value of M. verticillata revealed to possess anti-anemic and antihyperglycemic properties [26] . It is used as tops for salads and good for anaemic. It's utilized as demulcent and poultrice [28] .

Antioxidant Activity
The antioxidants are found abundantly in fruits and vegetables and protect the human body from oxidative stresses leading to damage of cells, diseases and other severe disorders [32] . According to the report, in comparison with Mollugo species, M. pentaphylla and M. cerviana are more promising antioxidants than M. verticillata [26] . M. cerviana significantly inhibited free radicals by 84.12±1.06% at 400 μg/mL [33] . In addition, M. pentaphylla and M. cerviana require IC50 levels of 16μg/mL [34] and 99μg/ mL [35] respectively, when compared to M. verticillata at 405.86μg/mL [26] . However, M. verticillata is more potent than M. nudicaulis (IC50 1, 350μg/mL) [29] .

Antimicrobial Activity
With the increase of interest in antibiotics came an increase of interest in plants as a potential source of antimicrobial substances [36] . According to the literature searched, anti-microbial activity of M. verticillata (pH-5.47) showed active against gram negative bacteria (Escherichia coli) using saline extract than gram positive bacteria (Staphylococcus aureus) [37] .

Antihyperglycemic Activity
With respect to multidrug resistance of Mycobacterium tuberculosis and active infection in people accompanied with HIV infection, there is a need for discovery and production of novel effective drugs against TB is felt [38] . Though the plant is responsible for the hyperglycemic effects more research has to be carried out due to the fact that the plant possess phytoconstituents that are capable of reducing blood glucose levels. However, additional investigations are required to address the exact mechanism by M. verticillata lowering blood glucose levels using in vivo studies.

Immunomodulatory Effect
The only research work carried out in immunomodulatory effect of M. verticillata in in vivo revealed to be promising and showed that ethanolic extracts (EE) could directly increase NO (Nitric Oxide) release by peritoneal cells, but reduces the immune response of these cells when treated with BCG antigen and Mycobacterium tuberculosis whole antigen (TB) [11] . Ferreira et al. (2003) reported that NO production by cells treated with BCG and EE was similar to that observed in control cells (BCG= 8.30μM and BCG + Mollugo= 5.09μM) [11] . Though the extract could not reverse the effect of TB it showed effective in reducing the stimulus. Decrease in NO production was about 35 % (TB= 12.37μM and TB + Mollugo= 8.01μM). The immuno stimulatory effects obtained using in vitro studies were confirmed in in vivo studies for some of the plant species such as Mollugo verticillata, Phoradendron serotinum and Petiveria alliacea [39] . Immunomodulatory effect using in vitro studies of M. verticillata revealed NO production (1.6 fold) at 25μg/mL using murine peritoneal primary macrophages co-cultures with Mycobacterium tuberculosis [48 h] and H2O2 production (0.4 fold) at 2.9μg/mL with murine primary peritoneal macrophages [24 h] compared to control cells [40] .

Importance of Invitro Studies
Efforts were made to optimize the concentrations of various plant growth regulators (PGRs) for in vitro growth of plant regeneration. A lot of research works were reported for Mollugo species, especially in M. nudicaulis Lam plant. The highest regeneration induction of about 88% of friable callus was observed on MS medium containing 4.44μM 6-BAP (Benzylaminopurine), 4.65μM kinetin, 2.69μM NAA (Naphthaleneacetic acid) and 0.91μM thidiazuron [41] . This plant can be used for in vitro growth responses and can be proved that hypocotyl explants can be best for callus induction. To date, only two C3-C4 intermediate species with a cosmopolitan distribution in warm climates, M. nudicaulis L and M. verticillata L., have been reported [42] .
Additionally, M. verticillata plant extract possesses therapeutic activities which are used in traditional medicine that can be used for enhancing the medicinal importance. This tissue culture could be used for year-round availability of the plant as well as allowing for comparative analysis of the functional anatomy of the in vitro grown plants and parent plant.

CONCLUSION
Mollugo verticillata (L.) is a medicinal herb used in traditional medicine which possess to be effective as antimicrobial, antioxidant and immunomodulatory activity. The exact bioactive compound and their mode of action is to be clearly studied and identified. Most of the researches on this plant extracts are not sufficient enough to clearly show any pharmacological activity like antiinflammatory and anti-tumour activity. In the drug improvement process, identification and characterization of bioactive compounds are necessary with current research.
These metabolites can be produced from plants and in vitro developed cultures which could be the source for an alternative one. Production of useful metabolites can be achieved which underlie the role and importance along with exact mechanism from the plant using elicitation method. Reports suggest that in vitro developed cultures have the potential to accumulate greater amount of secondary metabolites compared to field grown plant. In the current study, literature on M. verticillata and its compounds will help the researchers for further studies.

ACKNOWLEDGEMENT
The authors would like to thank the students, the administration and the Department of