CATHARANTHUS ROSEUS AND PROSPECTS OF ITS ENDOPHYTES: A NEW AVENUE FOR PRODUCTION OF BIOACTIVE METABOLITESHTML Full Text
CATHARANTHUS ROSEUS AND PROSPECTS OF ITS ENDOPHYTES: A NEW AVENUE FOR PRODUCTION OF BIOACTIVE METABOLITES
Meenakshi Koul, Neha S. Lakra, Ramesh Chandra and Sheela Chandra*
Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi- 835 215, Jharkhand, India
ABSTRACT: Catharanthus roseus is a medicinal herb found in many tropical and subtropical regions around the world. This plant produces a diverse array of secondary metabolites that are pharmaceutically important like vinblastine and vincristine used as chemotherapeutic agents in the treatment of several types of cancers. Low yield of these vinca alkaloids from the plant in vivo and the challenges to meet their high demand worldwide led researchers to develop various in vitro techniques like hairy root culture, callus cultures, shoot cultures, metabolic engineering and regulation studies to increase their production. The present review gives an account of the various phytochemicals derived from the plant and the pharmacological aspects of secondary metabolites studied. Present review also highlights the biotechnological prospects of an efficient and alternative means of production of valuable metabolites from Catharanthus roseus and also from rich microflora residing inside the plant tissues. It gives an emphasis on the need of exploration of diverse niches of endophytes.
Vinca alkaloids, Endophytes, Anti-tumor activity, Antidiabetic activity, Hypotensive activity
INTRODUCTION:Catharanthus roseus is a medicinal plant belongs to the family Apocynaceae native and endemic to Madagascar. The plant is also known by the names such as Vinca rosea, Ammocallis rosea and Lochnera rosea. The plant has been put to traditional use for the treatment of a wide variety of ailments worldwide since ages 1. The plant bears active phytoconstituents and exhibits various pharmacological activities like antidiabetic, antioxidant, anti-hypertensive, antimicrobial, cytotoxic etc. Catharanthus roseus produces a spectrum of terpenoid indole alkaloids (TIAs) vinblastine and vincristine, the anticancer lead molecules.
Being a source of these important secondary metabolites, an extensive study has been carried out on C. roseus. The present review provides a description of the secondary metabolites derived from this plant, its pharmacological activities, the biotechnological approaches undertaken to enhance the production of TIAs and the prospects of potential endophytes residing inside the host tissue.
Alkaloids: C. roseus is known to be a source of about 150 active alkaloids out of which vincristine, vinblastine and vindiscline are of prime importance because of their use in the treatment of Cancer 2. Vinca alkaloids vincristine and vinblastine are used in chemotherapy with vincristine being used for acute lymphocytic leukemia, both Hodgkin and non-Hodgkin lymphomas and vinblastine being used as the major component in chemotherapy for germ cell, breast, bladder and some types of brain malignancies3.
Vinblastine and Vincristine shown in (Figure 1) are anti-tubulin drugs that act by suppressing the spindle microtubule dynamicity in the cells during mitosis thereby arresting cell division and causing cell death 4.
FIGURE 1: ANTI LEUKEMIC ALKALOIDS ISOLATED FROM C. ROSEUS
Vinblastine and vincristine have been isolated in a pure form from C. roseus L. Don by the use of several chromatographic techniques like vacuum liquid chromatographic column on silica gel: aluminium oxide (1:1) mixed bed vacuum liquid chromatography (VLC), charcoal column, and finally purified by centrifugally accelerated radial chromatography (Chromatotrone) 5. Several other methods like high performance liquid chromatography 6, 7 and supercritical fluid extraction8 have also been devised to efficiently quantify these alkaloids in the plant.
Vinblastine and vincristine are the dimers formed by the coupling of Monoindole alkaloids such as catharanthine and vindoline found abundantly inthe aerial parts of the plant 9. The biosynthetic pathway of these alkaloids as in (Figure 2) has been found to be under strict developmental regulation in the plant10. Various studies on the regulation of the biosynthetic pathways as summarised in Table 1 revealed that terpenoid- indole alkaloid biosynthesis is subjected to different enzymatic and genetic regulation in the plant system.
FIGURE 2: TERPENOID INDOLE ALKALOID BIOSYNTHESIS IN PLANT SYSTEM
The enzymes are abbreviated as follows: TDC – Tryptophan decarboxylase, STR – Strictosidine synthase, SGD – Strictosidine glucosidase, T16H– Tabersonine 16-hydroxylase, NMT - 16-methoxy-2,3-dihydro-3-hydroxy tabersonine N-methyl transferase, D4H - Vindoline-4-hydroxylase, DAT- Deacetylvindoline O-acetyltransferase
TABLE 1: STUDIES ON ENZYMES INVOLVED IN TIAS BIOSYNTHESIS IN CATHARANTHUS ROSEUS
|Enzymes from Catharanthus roseus cell suspension cultures that couple vindoline and catharanthine to form 3′, 4′- anhydrovinblastine.||Endo et al. 11|
|Developmental regulation of enzymes of indole alkaloid biosynthesis in Catharanthus roseus.||Luca et al. 12|
|Isolation and characterization of a 2-Oxoglutarate dependent dioxygenase involved in the second-to-last step in vindoline biosynthesis.||Carolis et al. 13|
|Phytochrome is involved in the light-regulation of Vindoline biosynthesis in Catharanthus.||Aerts and Luca 14|
|Strictosidine synthase from Catharanthus roseus: purification and characterization of multiple forms.||Waal et al. 15|
|Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells.||Rischer et al. 16|
|Rapid identification of enzyme variants for reengineered alkaloid biosynthesis in Periwinkle.||Bernhardt et al. 17|
|A vacuolar class III peroxidase and the metabolism of anticancer indole alkaloids in Catharanthus roseus.||Sottomayor et al. 18|
|Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis.||Liscombe et al. 19|
Further, subcellular localization of these enzymes is also implicated in the regulation of the TIA biosynthetic pathway. Tryptophan decarboxylase and strictosidine synthase involved in the synthesis of strictosidine are both found in the cytosol.
16-methoxy-2, 3-dihydro-3-hydroxytabersonine-N-methyltransferase which catalyses the vindoline biosynthesis are localized in the chloroplasts of leaves.
Acetyl-coenzyme-A-deacetylvindoline-O-acetyl transferase catalysing the last step in vindoline biosynthesis is also a cytoplasmic enzyme 20. Most recently it has been reported that the entire production of catharanthine and vindoline occurs inside young leaves where the former accumulates in the leaf wax exudates and the latter within the leaf cells thus making leaves of this plant an important source of chemotherapeutic drugs 21.
The chemical synthesis involving direct coupling of vindoline and catharanthine and asymmetric total synthesis of vindoline and vindorosine based on a unique intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles have also been studied as a means for the production of terpenoid indole alkaloids like vinblastine, vincristine 22, 23.
Polyphenolics: Study of non-coloured phenolics from seeds, stems, leaves and petals of C. roseus and evaluation of their antioxidant activity led to the characterization of three caffeoylquinic acids and some flavonol glycosides with structures as in Figure 3. The scavenging ability of different plant matrices was assessed and a concentration-dependent protective effect was observed for seeds and tissues, with petals found to be most active followed by seeds and leaves, indicating their potential for use in food, pharmaceutical and cosmetic industries 24.
FIGURE 3: CHEMICAL STRUCTURES OF THE PHENOLIC COMPOUNDS IDENTIFIED IN C. ROSEUS
Anthocyanins: The production of anthocyanins has been described in vivo as well as in vitro from C. roseus. The major anthocyanins have been identiﬁed as the 3-O-glucosides, and the 3-O-(6-O-p-coumaroyl) glucosides of hirsutidin, malvidin and petunidin shown in Figure 4, respectively both in vivo and in vitro plant cell cultures 25. Besides these the presence of tricin, a flavone, was reported in the mature C. roseus petals 26.
FIGURE 4: ANTHOCYANINS FOUND IN C. ROSEUS
Steroids: Studies have shown that crown gall cells of octopine and nopaline-types derived from C. roseus (L.) G. Don produce brassinosteroids with the main components identified as brassinolide and catasterone. Brassinosteroids the steroidal growth-promoting plant hormones have been found to be useful in agriculture for increasing crop production, and improving stress resistance of crops against drought, chilling and pesticides 27.
Flavonoid glucosides: Four new flavonoid glucosides, 3’,4’-di-O-methylquercetin-7-O-[(4”→13”’)-2”’,6”’,10”’,14”’-tetramethylhexadec-13”’-ol-14”’enyl]-β-D-glucopyranoside, 4’-O-methyl kaempferol-3-O-[(4’’→13”’)-2”’,6”’,10”’,14”’-tetramethylhexadecane-13”’-olyl]-β-D-gluco pyranoside,3’,4’-di-O-methylbutin-7-O-[(6”→1”’)-3”’,11”’,-dimethyl-7”’-methylenedodeca 3”’, 10”’ dienyl]-β-D-glucopyranoside and 4’-O-methylbutin-7-O-[(6”→1”’)-3”’,11”’,-dimethyl-7”’-hydroxymethylenedodecanyl]-β-D-glucopyranoside were isolated from the methanol extract of C. roseus hairy roots for the first time. These new flavonoids were shown to inhibit MMP-9 activity and TNF-α production in THP-1 cells implying to their use as potential anti-inflammatory medication 28.
Iridoid glucosides: C. roseus is known to accumulate monoterpene indole alkaloids that are derived from the coupling of tryptamine and iridoids like loganin and secologanin (Figure 5) 29. The distribution of these iridoids at sub-cellular levels was studied in secologanin accumulating C. roseus cells and secologanin was found to be stored exclusively in the vacuoles 30.
FIGURE 5: IRIDOID GLUCOSIDES FOUND IN C. ROSEUS
Novel metabolites from cell cultures of C. roseus: Catharanthus roseus is not only an important source of the metabolites discussed above but has also been studied as the source of some novel active metabolites.
Some of the novel metabolites obtained from the cell cultures of C. roseus and the approaches used to produce them are discussed in Table 2.
TABLE 2: NOVEL METABOLITES FROM C. ROSEUS CELL CULTURE
|Metabolite||Function||Type of culture||Reference|
|Phosphatidate kinase||Enzyme of phospholipid metabolism||Plasma membranes of suspension cultured Catharanthus roseus cells||Wissing et al. 31|
|Trichosetin||Antibiotic||Dual culture of Trichoderma harzianum and Catharanthus roseus callus||Marfori et al. 32|
|Phytic acid||Storage of phosphorus, mRNA export, chromatin remodeling||Suspension cultured cells of Catharanthus||Mitsuhashi et al. 33|
Antidiabetic activity: Study of a dichlormethane: methanol extract (1:1) of leaves and twigs of C. roseus in Streptozotocin-induced diabetic rat models exhibited hypoglycemic activity with the improvement in decreased enzymic activities in liver of diabetic animals. Increased levels of lipid peroxidation caused during oxidative stress were also normalized by extract treatment 34.
The leaf juice of C. roseus showed a dose-dependent reduction in blood glucose in both normal and diabetic rabbits when compared to the standard drug, glibenclamide. The mechanism of action was probably due to enhanced secretion of insulin from the ß-cells 35.
Study of C. roseus, Azadirachta indica and Allium sativum showed significant antidiabetic activity for all three medicinal plants compared with the patent drug glimepride supporting their usage as herbal medicines for the diabetes by Ayurvedic physicians36. An investigation to study the impact of C. roseus leaves on the management of diabetes mellitus in about 20 type-2 diabetics residing in Dharwad city revealed a significant reduction in the fasting blood glucose, post prandial blood glucose, total cholesterol, low density lipoprotein cholesterol and triglyceride levels of the diabetic subjects 37.
A study carried out to investigate the antidiabetic and hyperlipidemic potential of C. roseus on alloxan induced diabetes in male albino rats revealed the therapeutic value of the aqueous flower extracts of C. roseus to combat the diabetic condition in rats 38.
Anti-tumor activity: A U.S. government screening program incidentally discovered C. roseus alkaloids vinblastine and vincristine, as well as some synthetic analogs as highly toxic chemotherapy drugs 39. Semi synthetic analogs, vinorelbine (VRLB) and vindesine (VDS), obtained from the active compounds showed potential activity against leukemias, lymphomas, advanced testicular cancer, breast cancer, lung cancer and Kaposi’s sarcoma in combination with other chemotherapeutic drugs 40.
Vinflunine, a bifluorinated derivative of vinorelbine exhibits a superior anti-tumor activity compared to other vinca alkaloids viz. vinorelbine and vinblastine. The mechanism of mitotic block is unknown but it is hypothesised that the anti-tumor activity is due to the decrease in microtubule dynamicity during mitosis and the increase in time centromere spends in the resting state during cell cycle. This novel vinca alkaloid is currently under Phase II clinical trials 41.
Cytotoxic activity: C. roseus was investigated for its cytotoxic activity by using MTT assay against Human Colorectal Carcinoma cell line (HCT 116). The study showed dose dependent cytotoxic activity of the methanol extract of C. roseus leaves with the chloroform extract showing the highest activity 42. The aqueous extract of C. roseus leaves standardised to Vinblastine was found to inhibit the proliferation of Jurkat cell line indicating the efficacy of the extract for modulating normal and transformed immune cells in leukemia patients 43. Three new dimeric indole alkaloids isolated from the whole plants of C. roseus have been evaluated for their cytotoxic activities against human breast cancer cell line MDA-MB-231 44.
Antimicrobial activity: Ethanol extract of the C. roseus flowers was studied for its wound healing potential in Sprague Dawley rats and the study showed that the extract had properties rendering it capable of promoting accelerated wound healing activity. Besides this the increased wound contraction and tensile strength, increased hydroxyproline content and antimicrobial activity further supported the topical use of C. roseus in wound treatment and management 45.
Crude extracts from different parts viz leaves; stem, root and flowers of C. roseus were tested for antibacterial activity. The leaf extract showed significantly higher activity suggesting that bioactive compounds of C. roseus can be a potentially exploited as antibacterial agents. Gram (-) strains were found to be more sensitive than the Gram (+) bacteria 46.
A study conducted to determine the antibacterial activity of crude extracts from different parts (leaves, stem, root and flower) of C. roseus against several bacteria of clinical significance indicated that the extracts prepared from the leaves showed better efficacy, the ethanolic extracts were more active against almost all the test microbes and Gram-positive bacteria were found to be more sensitive than the Gram-negative ones 47.
The plant parts, leaves, stems, roots and flowers of two varieties of Catharanthus roseus (L.) G. Don. "rosea" and "alba" were tested for their antibiogram by using different solvents (methanol, acetone and ethyl acetate). The variety “rosea” was found to have a better antibiogram than the alba variety.
Of the three solvents ethyl acetate extracts of different plant parts were found to have best antibiogram followed by methanol and acetone extracts 48.
In a study aimed to investigate some of the anti-microbial properties of C. roseus against microorganisms like Pseudomonas aeruginosa NCIM 2036, Salmonella typhimurium NCIM 2501, Staphylococcus aureus NCIM 5021 it was found that the extracts from the leaves of this plant can be used as prophylactic agent in many of the diseases, which sometime are of the magnitude of an epidemic 49. The leaf extract of C. roseus has also been shown to have significant fungitoxic activity against Macrophomina phaseolina and Sclerotium rolfsii the causative agents of the root rot disease in chickpea (Cicer arietium L.). The extracts strongly inhibited the mycelial growth in both the fungi at 50, 75 and 100% concentration when compared with the control50.
In a study to explore the antiplasmodial potential of C. roseus L, Coccinea grandis, Thevetia peruviana, Prosopis juliflora, Acacia nilotica, Azadirachta indica (Abr. Juss) and Morinda pubescens, the bark extract of A. indica (Abr. Juss) was found to have excellent antiplasmodial activity followed by leaf extract of A. indica (Abr. Juss) and leaf extract of C. roseus L 51.
Antioxidant potential: The effects of triadmefon treatment, a triazole compound on the antioxidant potentials and root alkaloid ajmalicine content were studied in two varieties of C. roseus, rosea and alba. The treatment with triadimefon increased the antioxidant potential as well as the indole alkaloid ajmalicine (more in the rosea variety than the alba variety) content. Results suggested that triadimefon may be a useful tool for increasing alkaloid production in medicinal plants 52.
A study to comparatively evaluate the antioxidant potential of ethanolic extracts of the roots of the two varieties of C. roseus and C. alba using different systems of assay, e.g. Hydroxyl radical-scavenging activity, superoxide radical-scavenging activity, DPPH (2,2-diphenyl-1-picryl-hydrazyl) radical- scavenging activity and nitric oxide radical inhibition method was performed. The results revealed that the root extracts prepared in ethanol exhibited satisfactory scavenging effect in all the radical scavenging assays in a concentration dependent manner and C. roseus showed more antioxidant activity than Catharanthus alba 53.
Hypotensive activity: The leaf extracts of C. roseus were investigated for the hypotensive and hypolipidemic activity in adrenaline induced hypertensive rats in a study. C. roseus leaf extract was found to have significant effect on each cardiovascular parameter after investigation with regard to hypotensive and hypolipidemic effect 54. The dry leaf powder of C. roseus was investigated for its antihyperlipidemic and antioxidant efficacy in male albino Wistar rats. The results of the study suggested that C. roseus possesses a significant antihyperlipidemic and antioxidant efficacy by attenuating the biochemical and physiological alterations in Streptozotocin induced diabetic rats 55.
Anthelmintic activity: Study of leaves extract of C. roseus showed potent antihelmintic activity in experimental adult earthworm Pheretima posthuma with the decrease in death time as the concentration increased. In the study, the control drug Piperazine citrate showed more potent anthelmintic activity compared to the methanol, aqueous, ethanol and ethylacetate extract 56. The anthelmintic property of C. roseus was evaluated using Pheretima posthuma as an experimental model and Piperazine citrate as the standard reference.
Among the various test concentrations, ethanol extract 250 mg/ml showed significant anthelmintic activity with death time of 46.33 min as compared to the standard drug at 50 mg/ml that showed paralysis at 31.33 min and death time as 40.67 min. The investigation thus revealed that ethanol extract of C. roseus showed significant antihelmintic activity against Pheretima posthuma supporting the ethnomedical claims of C. roseus as an antihelmintic plant 57.
Neuroprotective activity: A study was done to investigate the possible neuroprotective effect of C. roseus leaf extract against streptozotocin induced hyperglycaemia in the rat brain demonstrated that C. roseus leaf extract is an effective neuroprotective agent against diabetic oxidative damage as treatment with C. roseus reduced MDA, XO and Sorbitol DH production and increased glutathione levels significantly when compared to the streptozotocin induced diabetic-untreated rats 58.
Antifertility efficacy: Oral administration of C. roseus Linn, leaf extract leading to widespread testicular necrosis, hyalinization of tubules and sertoli cell-only-Syndrome, notable reduction in glycogen and fructose levels in reproductive tissues confirmed the antifertility properties of C. roseus extract 59. The petroleum ether extract of C. roseus leaves inhibited the estrogen induced gain in the uterine weight when administered along with estradiol into the female albino mice thus proving to be highly effective in suppressing pregnancy 60.
Biotechnological approaches to enhance in vitro production of terpenoid indole alkaloids from C. roseus: Catharanthus roseus has been of much interest among the scientific and medical communities because of its pharmacological potential. The interest can be traced back to the mid-1950, when researchers began to study the plant for its reported antidiabetic properties. The pharmacological potency of the plant as discussed earlier is due to its varied active constituents and the plant being a sole commercial source of anti-cancer alkaloids vincristine and vinblastine 61 has made it an important subject of research.
Most of the scientific research done on C. roseus in the past years had been focussed towards the isolation and characterisation of TIAs, testing their bioactivity and study of their biosynthetic pathways. Low yield of these vinca alkaloids from the plant in vivo (0.0005%) 62 and the challenge to meet their high demand worldwide (3kg/annum) has led to the development of various in vitro techniques like hairy root culture, callus cultures, shoot cultures for their increased production. Besides these classical tissue culture techniques, metabolic engineering aspects have also been studied to improve the production of terpenoid indole alkaloids 63.
Metabolic and biochemical engineering have been studied as a perspective for the creation of new cell lines producing TIAs in large scale bioreactors combined with efficient upstream and downstream processing 64. Recently, a study to investigate the effect of various elicitors of hydroxylase, peroxidase, acetyltransferase and inhibitors of oxygenase on regulation of vinblastine biosynthesis in cell suspension cultures of C. roseus showed Hydrogen peroxide, Acetyl CoA, Benzotriazole to be very effective in enhancing the production of vinblastine65.
Table 3 summarises some of the biotechnological approaches used to increase the terpenoid indole alkaloid production.
TABLE 3: BIOTECHNOLOGICAL APPROACHES TO INCREASE TIAS PRODUCTION
|Plant species/family||Method Used||Yield||References|
|Catharanthus roseus(Apocyanaceae)||Biofilm culture(biofilm thickness-6mm)||% Alkaloids – 0.18||Kargi et al. 66|
|Catharanthus roseus immobilized cells||Serpentine - 300 μg/L||Archambault et al. 67|
|Hairy root culture (indole alkaloids)||2- to 3-fold higher than untransformed culture||Cau-uitz et al. 68|
|Cell suspension culture (addition of loganin and tryptamine)||TIAs-350 mmol/L||Whitmer et al. 69|
|Catharanthus roseus(Apocyanaceae)||Cell suspension culture + ChemicalsBetaine
Tetramethyl ammonium bromide
|Ajmalicine - 55.4 mg/lAjmalicine - 26.8 mg/l
Ajmalicine - 63.6 mg/l
Serpentine – 32mg/l
Serpentine - 8.5 fold increase
Serpentine – 16 mg/l
Ajmalicine – 23 mg/l
Ajmalicine – 31 mg/l
Ajmalicine – 60 mg/l
Catharanthine – 24 mg/l
Serpentine – 19mg/l
|Zhao et al. 70|
|Cell suspension culture (addition of 10.0 mmol/L Sodium nitroprusside)||Total Catharanthine 40.3 mg/L||Xu et al. 71|
|Applicationof Gibberellic acid (1000 g m–3)||Total alkaloids [% DM] 3.44||Srivastava and Srivastava 72|
|Combined treatment of Arbuscular Mycorrhizal Fungi (AMF) and P2O5 (200 kg P2O5/ha+AMF)||Ajmalicine (1.22±0.66, 1.68±0.44 mg/g/plant)||Karthikeyan et al. 73|
|Suspension culture(UV B irradiation)||Catharanthine – 0.12 ±0.0054 mg/g DWVindoline – 0.06 ± 0.0023 mg/g DW||Ramani and Jayabaskaran 74|
|Hairy root cultureMetabolic engineering||Total TIAs (9.51mg/g DW)||Zhou et al. 75|
|Callus||Vincristine (20.38 mg/g)||Kalidass et al. 76|
|Hairy root cultureOver expression of transcription factor CrWRKY1
Repression of transcription factor CrWRKY1
|Serpentine - 291.5 6 ± 73.2 μg/g DW
Ajmalicine - 15.4 6 ± 1.6 μg/g DW
Catharanthine - 100.2 ± 15.1 μg/g DW
Tabersonine - 19.3 6 ± 1.6 μg/g DW
|Suttipanta et al.77|
|Co-cultivation in 1/2 MS medium containing 100 μ Macetosyringone||Vindoline1.42 ~ 2.72 μg/mg (DW)||Wang et al. 78|
|Hairy root culture (co-cultivation with A. rhizogenes A4. B5 medium)||Catharanthine 0.17 mg/g FW||Zhou et al. 79|
|Cell suspension cultureRegulation by elicitors and inhibitors||Tabesonine (9.02mg/g DW), Vindoline (0.42mg/g DW)Vinblastine (0.81mg/g DW)||Guo et al. 65|
A new avenue for production of bioactive metabolites: Despite these continuous efforts, the desired level of production of these metabolites has still not been achieved at optimum level, thereby making it necessary to bioprospect their new sources. Taking into consideration the limitations associated with the production of these metabolites in vivo and the need to preserve the world’s ever-diminishing biodiversity, a microbial source of a valued product may be easier, sustainable and more economical for the production of valuable metabolites, effectively reducing their market price. Endophytes, the microbes that colonize the internal tissues of the plants without causing any overt negative effects, could thus be the potential sources of these valuable bioactive metabolites 80. The endophytes are a diverse group of microbes owing to the fact that almost all vascular plants examined to date have been found to colonize these microbes 81, 82. Due to varied ecological niches of C. roseus, there is also a probability of diversity in endophytic localisation inside the plant tissues. The endophytes are sources of bioactive compounds like alkaloids, terpenoids, flavonoids, steroids etc that have importance in medicine, agriculture and industries as well 83, 84. Table 4 gives an account of the bioactive compounds obtained from the endophytes islolated from Catharanthus roseus till date.
TABLE 4: BIOACTIVE COMPOUNDS OBTAINED FROM ENDOPHYTES ISOLATED FROM C. ROSEUS
|Endophyte||Plant part used||Compound||Bioactivity||Reference|
|Alternaria sp.||Inner bark||Vinblastine||Antitumor||Guo et al. 85|
|Fusarium oxysporum||Stem||Vincristine||Antitumor||Zhang et al. 86|
|Unidentified||Leaves||Vincristine (0.205 µg/L)||Antitumor||Yang et al. 87|
|Pestalotiopsis sp.||Leaves||Taxol (92µg/L)||Antitumor||Srinivasan and Muthumary 88|
|Vrb46 similar to Bacillus coagulans||Stem||-||Antimicrobial||Roy and Banerjee 89|
|Actinomycetes sp.||Leaves||-||Antimicrobial||Kafur and Khan90|
Endophytes isolated from C. roseus not only yield these valuable therapeutic molecules but have recently been studied to improve the in planta content of terpenoid indole alkaloids like serpentine, ajmalacine, vindoline and vinblastine. The study showed that the bacterial endophytes isolated from this plant identified as Staphylococcus sciuri and Micrococcus sp.could possibly be used as bio-inoculants to increase the plant biomass and the content of key terpenoid indole alkaloids within the plant thus providing an efficient and economic means to overcome the gap between high demand and low supply of these vinca alkaloids globally 91.
Conclusion: Catharanthus roseus is an important medicinal plant with a wide range of uses. The dried plant extracts contain many alkaloids of medicinal use. These alkaloids are produced in very small quantities inside the plant although attempts have been made over the past years to increase their production through various biotechnological applications. The plant has been proven useful not only in the field of medicine but has also been recently put into use for the phytoremediation of radiocesium 137Cs from low level nuclear waste 92.
The leaves of this plant have been found to be of immense medicinal use as most of the pharmacological activities of this plant are attributed to its leaves. So the cultivation as well as the conservation of this plant must be promoted on a large scale. Besides this alternative means, that are less time consuming, sustainable and more economical, must be developed and adopted for the production of these active constituents.
In the present times, when the emphasis is being placed on the use of natural materials in the control and treatment of various diseases and infections because of the undesirable side effects of synthetic drugs there is a need for further research especially on bioactive compounds, their production from alternative sources, methods for increasing their production, herbal remedies, effectiveness of plants for various uses and bioprospecting new sources of natural bioactive products which can provide unlimited scope for the development of new drug leads. Endophytes could thus be exploited as the sources of the valuable secondary metabolites of medicinal, agricultural and industrial importance.
Owing to the huge microbial biodiversity of endophytes, these are still the less investigated group of microorganisms that need to be explored for their huge potential of being used as the sources of pharmacologically active therapeutic lead compounds.
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How to cite this article:
Koul M, Lakra NS, Chandra R and Chandra S: Catharanthus roseus and prospects of its Endophytes: A new avenue for production of bioactive metabolites. Int J Pharm Sci Res 2013: 4(7); 2705-2716. doi: 10.13040/IJPSR. 0975-8232.4(7).2705-16
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Meenakshi Koul, Neha S. Lakra, Ramesh Chandra and Sheela Chandra*
Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi- 835 215, Jharkhand, India
05 March, 2013
07 May, 2013
24 June, 2013
01 July, 2013