A COMPREHENSIVE REVIEW ON COSTUS PICTUS D. DON

A COMPREHENSIVE REVIEW ON COSTUS PICTUS D. DON

G. M. Radha Devi

Department of Botany, Jnanabharathi Campus, Bangalore University, Bangalore - 560056, Karnataka, India.

ABSTRACT: Costus pictus is rhizomatous medicinal herb, commonly known as “Insulin plant,” well known for its therapeutic properties. Many important and beneficial aspects of C. pictus are reported, which includes anti-diabetic, anti-microbial, anti-cancer, anti-oxidant, anti-fertility, anti-helminthic, diuretic, anti-inflammatory properties. The present review focus on the literature survey based on their occurrence, nature of plant, distribution, pharmacologically important bio-active compounds, utilized in the treatment of diabetes and related disorders. Along with micropropagation of Costus pictus under the aspectic condition and molecular approaches towards the treatment of disorders and different pathways involved. This summarized review focus on the future scope of research and development for synthesis of much effective dose and dosage period to formulate the therapeutic potential of Costus pictus and their phytoconstituents.

Anti-diabetic, Anti-bacterial, Anti-microbial, Costus pictus, Insulin plant

INTRODUCTION: Medicinal plants being an herbal remedy in both developing and developed countries in the management of health care, globally 80% of the population relies on traditional medicine, since ancient times as major source of medicine in treating many diseases, Ayurveda, Unani, homeopathy, naturopathy. Natural products derived from plants on a large scale and attracted by many researchers due to less or no side effects. Costus pictus is commonly known as fiery Costus, step ladder or spiral flag or Insulin plant native to south and Central America and recently introduced in India for its valuable medicinal properties, oral consumption of leaf daily to cure diabetes and most widely spread across Kerala as an ornamental and daily culinary purpose ¹.

It’s used as folk medicine by tribal people of kolli hills of Namakkal district Tamil Nadu ². The field survey in Paithan Tehsil Aurangabad district found C. pictus new flora in Maharashtra ³ and similarly found in Odisha ⁴.

The first published record of Costus as taxa was found in Hortus malabaricus by Hendrick Andariaan Van Rheede (1678-1693) in Kerala. The family Zingiberaceae consists of nearly 53 genera largest family of the order Zingiberales over 1000 species and found abundant in South East Asia distributed mainly in tropics and subtropics of central distribution in Indo-Malayan region also extending through tropical Africa to central and South America ⁵. The family Costaceae consists of 4 genera and over 200 species. Costus is native of tropical areas of Asia, Africa, Australia, and the America ⁷. Costus under family Zingiberaceae, Costaceae is classified as Costideae by Engler & Prantl; sub family or as a tribe (Costeae) within Zingiberaceae. Thus genus Costus along with genera Dimerocostus (2 species), Monocostus (1 species) and Tapeinochilus (20 species) was separated from family Zingiberaceae to the family Costaceae due to fused staminode ⁷. Their molecular dating of cladogenic events combined with phylogeny-based bio-geographic analysis, Dispersal Variance Analysis (DIVA) and Chloroplast DNA data trnsL-F and transK. It has been separated from Zingiberaceae for its the significant arrangement of leaves, spiral phyllotaxy showy labellum unique character along with easily differentiable characters like essential oils and distichous arrangement of the leaves ¹.

The phylogenetic relationship, bio-geographic and pollination history of Costus sub genus by ITS and ETS regions, the sequence data of nuclear ribosomal DNA (18s-26s) shows monophyletic neotropical species radiations, having large, showy flowers visited by a euglossine bee or hummingbird ⁸. Costaceae has been mono-phylogenetic in origin when compared with the different taxonomic groups, by studying 65 taxa by their geographical and morphological diversity of the family ¹³ found their molecular characters in 3 major clades American, Asian, African, neo-tropical by comparing 5898 characters of 5827 molecular and 71 morphological characters of 67 taxa. It is a pantropical monocot family Costaceae (Zingiberaceae) approximately 120 species, it also shows recognizable differentiation from families including bananas (Musaceae) and ginger (Zingiberaceae) by it's well developed and sometimes branched aerial shoot with characteristic spiral monistichous (one-sided phyllotaxy) of leaves ¹⁰ belonging neotropical radiation bee pollinated ancestors.

C. pictus consists of various therapeutic properties, anti-diabetic mainly along with anti-bacterial, anti-cancerous, diuretic, anti-helminthic, anti-oxidant, anti-fertility, anti-glycation, etc. ¹¹ Along with these the methanol and ethanolic extract of C. pictus leaves known to exhibit significant enzymatic action on pepsin, α amylase, effect on mitochondrial enzymes, carbohydrate hydrolyzing enzymes; induce insulin production. The phytochemical investigation reveals the presence of major bioactive methyl tetracosonoate as a precursor for bixin production acts as an anti-diabetic property for leaves. The rhizome, stem, and flowers are rich in primary and secondary metabolites presence secondary metabolites like alkaloids, flavonoids, phenolics, saponins, terpenoids, tannins, steroids, etc along with trace elements. C. pictus now world widely accepted as an anti-diabetic plant as clinically trails on animal cells line in-vitro and in-vivo studies, and Pharmacoepidemiological survey suggests that consumption of one leaf daily known to reduce blood glucose level (Biospectrum 2013). Thus exploitation of this plant is increasing day by day, hence in-vitro propagation and production in mass have been carried out.

Pharmacological Properties: C. pictus used a folk medicine treating various chronic diseases due to the presence of major and minor phytochemical constituents as primary and secondary metabolites identification characterization of the chemical and bioactive components is carried out by many researchers. It has been reported that the saponified extract of leaf analysis by GC-MS revealed 18 major chemical compounds Table 1 major component in the ether fraction is bis(2’-ethyl hexyl)-1,2 benzene dicarboxylate. Presence of α-tocopherol as a cause of the anti-oxidant property of the leaf extracts ¹².

Different solvent extract of leaves stem and rhizome methanol extract exhibited maximum and pronounced anti-diabetic activity consists of β-L-Arabionopyranose methyl glycoside as a reference compound ¹³. The leaf of C. pictus shows the anti-diabetic property when treated on alloxan induced rats by the presence of various secondary metabolites in specific flavonoids compounds. Table 1 constitute for anti-diabetic and anti-oxidant activities ¹⁴. The leaf of C. pictus consists of calcium oxalate crystals as minute particles along with carbohydrates, triterpenoids, proteins, alkaloids, tannins, saponins, flavonoids sterols volatile oils. Powder microscopic study of leaf showed fragments of unicellular trichomes, hexacytic stomata, abaxial solitary bundle ¹⁵, and appearance of cuboidal solid crystals in all parts of C. pictus plant ¹⁶.

The LC-MS analysis of C. pictus extract found 4 major flavonoids along with 6 phenolic compounds Table 1 ¹⁷. The macro and microscopic study of C. igneus leaves found epidermis with anomocytic stomata, mesophyll cells with calcium oxalate crystals and fibers associated with parenchyma cells ¹⁸. The report on physicochemical and phytochemical screening of aqueous and ethanolic extract of C. pictus carried out as per the WHO guidelines found to contain many primary and secondary metabolites ¹⁹.

TABLE 1: LIST OF BIO-ACTIVE COMPOUNDS FOUND IN LEAF AND RHIZOME EXTRACT OF C. PICTUS

It is also reported that aqueous and ethanolic extracts of C. igneus stem with calcium oxalate crystals and isolated compounds like lupeol and stigmasterol ²⁰, also calcium oxalate monohydrate crystal growth was reduced and morphology of the crystals changed from hexagonal to bi-pyramidal form due to the inhibitory action of extracts. A bioactive compound like diosgenin a steroidal saponin has been isolated and quantified by HPLC method ²¹, isolated diosgenin was characterized by various parameters such as color, odor, pH, physical appearance solubility was reported by ²². The leaves are sour due to the presence of oxalic acid in the leaves and determination of oxalate oxidizes activity ²³.

Anti-diabetic Property: The leaves of C. pictus is medicinally important in treating hyperglycemic activity, the ethanolic and methanolic extracts when induced to streptozotocin and alloxan induced rats ^{24, 25, 26, 27, 14} showed a significant reduction in the blood sugar level. Along with the identification of trace elements like K, Ca, Cr, Mn, Cu, and Zn ²⁸ stimulates the antidiabetic property. The aqueous extract also reported that antidiabetic property on streptozotocin-induced diabetic rats and in-vitro pancreatic islet culture, oral administration of 250 mg/kg of C. pictus ²⁹. Effect of Carbohydrates hydrolyzing enzymes like α amylase and α glucosidase in aqueous extract showed the highest inhibitory effect at 100 mg/ml ^{30, 31}. In-vitro studies carried out on M1N6 monolayer, and M1N6 membrane integrity showed a concentration-dependent increase in insulin secretion and showed a direct effect on islets of β cells to stimulate insulin secretion ³².

Genomic analysis of C. pictus leaves shows solid molecular transcripts for bixin, ABA and geraniol and geraniol biosynthesis by Next-generation sequences base approach in contribution towards therapeutic properties and presence of a precursor to bixin a putative product of nor-bixin methyltransferases as anti-diabetic property ³³. The ethanolic extract of a leaf found to be anti-proliferative and cytotoxic at lower concentration and induced cell death in MOLT-4 cells ³⁴. The extract at a dose of 500mg/kg b/w shows the highest percentage of glucose lowering of blood glucose level compared with the reference compound β-L-arabinopyranose methyl glycoside ¹³.

Anti-microbial Activity: The essential oil obtained from C. pictus leaf showed anti-bacterial activity against gram +ve and gram –ve bacteria strains of Bacillus cerenus, Enterobacter facealis, Salmonella paratyphi, Escherichia coli, Protus vulgaris, Pseudomonas aeuroginosa, Serratic marcescens, Staphylococcus aureus, Staphylococcus faccalis, Klebisella pneumonia ³⁵. Similarly, rhizome extract when treated in different concentration Bacillus subtilis, Staphylococcus aureus and Escherichia coli and Pseudomonas aeurginosa showed significant anti-bacterial activity ³⁶ and Solmonella typhimrium ³⁷. As per the observation, Aspergillus nigar and Claviceps purpea fungal members had no significant with rhizome methanolic extract of C. pictus. The ethanolic leaf extract showed concentration-dependent activity on bacterial colonies along with identification of bioactive compound experimentally proved as antibacterial property.

Anticancer Property: The methanolic extract of C. pictus can induce apoptosis of bone cancer on MCF7 Breast cell and proved cytotoxic ³⁸. The ethanolic extract of C. pictus of leaves found to be anti-proliferative and cytotoxic at lower concentration and induce cell death in HT1080 fibrosarcoma cells ²¹. The bark extract of C. pictus has potential natural anti-oxidant activity against HT 29 and A549 cells ³⁹.

Anti-oxidant Activity: The leaf and rhizome extracts of C. pictus show the good anti-oxidant activity of about 89.5% and 90% at a concentration of 400µg/ml ²⁴ estimated by DPPH, β carotene, Deoxyribose superoxide anion, reducing power and metal chelating assay at different concentration. The chloroform extract of C. pictus leaf extract showed a high percentage of inhibition of lipid peroxidation radical scavenging activity on in-vitro goat liver and RBC ghost and identification of steroidal compound acts as a defense system on enzymes and radical scavengers ⁴⁰.

Leaf extracts show significant anti-oxidant and free radical scavenging activity were clinically tested against pre-oxidative damaged albino rats; it resulted that ethanolic leaf extracts significant reversal of reduction of GSH, SOD, and CAT and reduced significantly the levels of MDA. A biomarker for lipid peroxidation as dose-dependent acting as a defense system against anti-oxidative injury ⁴¹. The root and stem extract of C. igneus showed high anti-oxidant activity ¹⁴ also reported that methanolic extract has high bioactive components and active anti-oxidant property ^{42, 43}.

Anti-fertility: Ethanolic extract of C. pictus rhizome when treated to female rats at a dose of 200 and 400 mg/kg for 19 days, later studied with various parameters like percentage of pregnant female animals in each group, Mean live foetal number/pregnant female, mean foetal crown-rump length. Mean corpus luteum number/pregnant female and fertility index showed a decrease when compared to control. The rhizome extract has an active biomarker diosgenin a naturally occurring steroid saponin that acts as an anti-fertile index ⁴⁴.

Anti-helminthic: A comparative in-vitro evaluation of anthelmintic property of leaves and rhizome of C. pictus against albendazole standard drug, methanolic and aqueous extract of leaves and rhizome showed the significant anti-helminthic effect on Pheretima Posthuma earthworm ⁴⁵. The hydro-alcoholic effect of C. pictus rhizome showed significant activity at a dose level of 0.5, 0.75 and 1 g against a standard drug piperazine citrate ⁴⁶.

Diuretic Effect: The aqueous extract of C. pictus of leaves at 100 & 200 mg/kg b/w when treated on rats in comparison with furosemide at 4 mg/kg, C. pictus extract induced a natriuretic effect similar to furosemide drug also increase of sodium and potassium ion excretion in urine of rats ⁴⁷.

Anti-inflammatory Activity: The in-vitro assessment of anti-inflammatory activity showed a maximum percentage of inhibition at 400 mg/ml at 97.87% ³¹.

Hypothyroid: The leaf extract was extracted with 80% methanol showed a dramatic decrease in the thyroid stimulating hormone TSH and can be used as a potential source for resorting thyroid hormone levels and prevent biochemical complication due to thyroid hormone insufficiency. LC-mass spectrometry analysis showed the presence of pentacyclic trite pens α and β marines. DPPH 38.82 ± 1.26µg/ml IC ₅₀ 6.73 ± 0.15µg/ml, FRAP 2.98 ± 0.03mmol Fe²⁺ positive ascorbic acid 18.76 ± 0.38 mol Fe²⁺ g ⁴⁸.

Enzymatic Activities: The α amylase inhibitory activity of methanolic extract of C. igneus shows a significant amount of inhibition of amylase enzyme greater inhibition showed a higher concentration of 500µg help to prevent hyperglycemic problem ⁴⁹.  The α-amylase and α-glucosidase enzyme action were studied using in-vitro assay in C. pictus leaf using porcine pancreatic α-amylase with starch as a substrate, α-glucosidase inhibitory evaluation using p-nitrophenyl-α-D-Glucopyranoside (PNPG) as substrate fresh aqueous extract exhibited a strong inhibitory effect on α-glucosidase then α-amylase ⁵⁰. The study on pepsin enzyme, which shows close resemblance with HIV protease in proteolytic activity, pepsin used as a substitute for HIV protease inhibitory activity, the fresh hydro-alcoholic extract revealed the highest inhibitory activity ⁵⁰.

Synthesis of Nano-particles: The leaf extract of C. pictus when mixed with aqueous solution of silver nitrate changed into brown color due to the excitation of surface plasmon vibrations indicated the formation of methanolic extract of C. pictus silver nanoparticles (MECPAgNP’s) examined under UV visible spectroscopy analysis of nanoparticles showed the broadening of the peak indicated the particles are polydispersed at 420 nm. The average particle size 132-6 nm is polydispersity index 0.2480 and zeta value of 25.1mv with the peak area of 100% intensity. SEM image showed that the silver nanoparticles formed were spherical with an average size of around 100 nm ⁵¹.

Comparative study of the in-vitro antioxidant activity of methanolic extract of C. pictus and its silver nanoparticles (MECPAgNP’s) were studied by various methods, DPPH assay, H₂O₂ Scavenging activity, phosphor-molybdenum method, FRAP and reducing power assay. Total phenolic content, flavonoid content, vitamin C. The nanoparticle showed as dose-dependent reducing ability showed much better activity than the extract alone. The phenolic, flavonoid and vitamin C amount was higher in MECPAgNP’s then in MECP thus C. pictus can be used as biologically synthesized nanoparticles rendering more effective, exceptionally stable and also with minimum toxicity and cost-effective ⁵². The leaf extracts of C. pictus used for the synthesis of bio-compactable ZnO and MgO nanoparticles from the zinc nitrate by green process ⁵⁴.

Micropropagation: C. pictus is a medicinally important plant and fast disappearing, threatened species due to tremendous utilization of the leaf and plant parts for various therapeutic properties. It is a rhizomatous plant due to its poor seed viability; low rate of germination, reproduction is only by vegetative method and production of advantageous propagules. The need of this plant is great demand; thus conversation, and mass production of the same is important. It is reported that the when rhizome explants when cultured on MS medium with different concentration of benzyl adenine and kinetin maximum no of shoots were obtained in 2.5mg/l and kin 1mg/l. High frequency of rooting was obtained in rhizome explants produced shoots on half strength MS with IAA 1.5 mg/l ⁵⁵.

The nodal explants were treated with MS medium supplemented with 3-4µM BAP+0.2µM NAA and 0.6µM NAA+3µM BAP highest percentage of dormant bud were regenerated. Maximum shoot formation in 0.6µM NAA and 8µM BAP rooted on 1-12µM NAA and 3µM BAP. The maximum number of root found in 8µM NAA and 3µM BAP. The dormancy of the in-vitro raised plants was successively done by decapitating and culturing on MS medium with 0.6µM NAA, 7µM BAP and 5-13% sucrose. Rhizome when cultured on half strength MS medium 2-4µM NAA, 32µM BAP, micro rhizome formed in 9% sucrose ⁵⁶.

Similarly when nodal segments cultured on MS medium with 1-4mg/l BAP +0.1-6mg/l IAA, maximum propagation were observed on 2.7mg/l BAP and 0.2mg/l IAA ⁵⁷. It has been reported that when leaves were cultured on MS +2,4-D/KIN 1+0.5mg/l and IAA/BAP 1mg/l produced good callus, at 3% and 6% sucrose and pH 5.5 ⁵⁸. Similarly, when leaf and nodal explants produced callus in MS+0.5mg/l IAA and 2.5mg/l BAP. Induction of callus was also noticed by culturing on MS with IAA, KIN leaf callus was obtained MS+0.5 mg IAA +2mg BAP ⁵⁹. The Nodal segments when cultured on SH media with 1mg/l BAP +1mg/l IBA+25mg/l AdSO4. Rooting, regenerated of shoots were maximum ⁶⁰. Multiple shoots were obtained from stem nodal region when cultured on 1ppm NAA, 4ppm BAP and 10ppm urea, root induction found in 2ppm BAP+1ppm IAA as the best combination for root induction, maximum root length found in 1ppm NAA+4ppm BAP+10ppm urea ⁶¹. The leaf stem nodal and  rhizome explants of C. igneus when cultured on MS and LS showed maximum callus in BAP 0.4mg/l+KIN 0.2mg/l+NAA 0.1mg/l+ IAA (0.2mg/l)+ IBA (0.2mg/l) shoot regeneration on MS and LS medium with BAP 0.4mg/l+KIN 0.25mg/l+NAA 0.1mg/l+IAA 0.2mg/l ⁶².

Molecular Studies: C. pictus plant is well known as insulin plant, and economically important medicinal plant consists of the high value of secondary metabolites, bioactive compounds, and a remarkable number of flowering features. MicroRNA’s are a class of short (-21nucleotides) endogenous, non-coding RNA molecule plays a vital role in regulating gene expression. Thus computer-based homology approach to identify conserved miRNA in transcribed sequence assemblies (TSA) of C. pictus led us to identify 42 miRNA’s of 13 different families in C. pictus by PCR assays. Total of 109 potential target genes were identified miRNA’s that regulates several metabolic pathways. Total 42 homolog miRNA’s of 11 different families, namely miR166, miR394, miR168, miR172, miR169, miR858, miR167, miR5658, miR396, miR444, were observed. This finding helps in finding the growth pattern cellular developmental process, signal transduction, stress response, and ubiquitin-proteosome degradation pathways ⁶³.

The C. pictus species is reproduced by vegetative method thus much genetic variation is noticed when rhizomes of 3 different agro-climatic regions of Kerala Thiruvananthapuram, Ernakulam and Kannur studied based on their morphological, biochemical, gas and water vapor exchange and RAPD analysis. There was no significant difference in gas water vapor exchange parameters like net photosynthesis, stomatal conductance, transcription rat, and PSII efficiency measured by chlorophyll fluorescence did not show any marked difference in the respective samples. The RADP analyses using 40 primers and 10 decamers at 3 accessions did not reveal any genetic discrepancies ⁶⁴.

Similarly when C. pictus plant was collected from 15 different geographical regions of India, the RAPD and ISSR markers were selected with 25 RAPD and 20 ISSR primers, it generated 343 loci, 124 were polymorphic average of 4.96 loci/primer, whereas in ISSR primers 177 loci 77 were polymeric, average of 3.85 loci/primer. The similarity co-efficient ranged from 0.86-0.99, 0.84-0.95 and 0.86-0.96. The dendrogram graphically did not reveal much variation with a low level of divergence. Highest level of polymorphism in ISSR 42.47% and RAPD 35.57% were observed ⁶⁵.

CONCLUSION: Diabetes mellitus is a chronic disorder in recent times becoming a major treat for the human being worldwide; it is caused due to increased production of insulin from pancreas or inefficient utilization of insulin. The body cells losses its ability to utilize the production of glucose in the blood due to hormonal imbalance, in the earlier stages by the pancreatic disorder. Diabetes a complex disease due to the inhibitory action of consumption of carbohydrates, protein, fats, deficiency in secretion and utilization of insulin, due to the destruction of the immune system and reduces the efficiency of the pancreas cells.

There are many secondary metabolites as natural compounds like alkaloids, flavonoids, phenols, saponins, tannin, steroids, terpenoids, etc. act as a supplements for treating various therapeutic properties like anti-diabetes, anti-microbial, anti-cancerous, diuretic, anti-helminthic, anti-oxidant, anti-fertility, etc. thus plants acts as a novel drug for reduction of hyperglycemic to hypoglycemic condition. Plants act as a good source of medicine in the treatment of various types of diseases, there are many medicinal plants still too identified for their bioactive phyto-constituent, and active metabolites are obtained from plants due to plant-based drugs are more effective cost-effective and possess valuable compounds.

The traditional medicine obtained as a natural product shows very less or no side effects, thus it is believed that plants and plant-based products are very convenient and safe to be used in treating various disorders for mankind. The review on this present study gives a clear idea that C. pictus plant is very important medicinal plant grown in South India well grown easily grown as an ornamental plant can be utilized to reduce and maintain the blood glucose level in diabetic patients. Consumption of “a leaf day reduces high blood glucose, presence of bixin compound acts as the precursor for the anti-diabetic property. Costus pictus very popularly has known worldwide for its anti-diabetic properties in most of the world as well in India; diabetic patients are increasing tremendously, around 422 million adults were living with diabetes in 2014 when compared to 108 million in 1980. The rate of diabetic patients increased by 4.7% in 1980 to 8.5% in 2014. The diabetes patients are doubled since 1980 form 4.7% to 8.7% as per the survey of the World Health Organization (WHO). Thus, identification of many medicinal plants and study on therapeutic properties identification of bioactive compounds, a modern trend in the ear of science and research development is necessary and further investigation of valuable metabolites in this plant is necessary.

ACKNOWLEDGEMENT: The author would like to express her thanks to all facility, Department of Botany, Bangalore University, Bangalore and thanks for Manoj Kumar, GE Health care. UGC commission for Financial grants.

CONFLICT OF INTEREST: The authors declare that there is no conflict of interest regarding this review paper.

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    How to cite this article:

    Devi GMR: A comprehensive review on Costus pictus D. Don. Int J Pharm Sci & Res 2019; 10(7): 3187-95. doi: 10.13040/IJPSR.0975-8232.10(7).3187-95.

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