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R e v i e w A r t i c l e

UP-TO-DATE REVIEW ON THERAPEUTIC INTERIOR OF

CATHARANTHUS ROSEUS; FOR ANTICANCER AND

ANTIDIABETIC ACTIVITIES

Ashwani Kumar1, Richa Malik

1, Pinki Giri

1, Nazia Parveen

1, Shweta .

1

1Faculty of Bioscience, Shri Ram College Muzaffarnagar, UP-251002 India

Correspondence should be addressed to Ashwani Kumar

Received April 22, 2015; Accepted May 10, 2015; Published June 25, 2015;

Copyright: © 2015 Ashwani Kumar et al. This is an open access article distributed under the Creative Commons

Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the

original work is properly cited.

Cite This Article: Kumar, A., Malik, R., Giri, P., Parveen, N., Shweta. (2015). Up-to-date review on therapeutic

interior of catharanthus roseus; for anticancer and antidiabetic activities. Journal of Phytomedicine, 1(1).1-13

ABSTRACT

Cathranthus roseus comprise a group of alkaloids mainly vincristine, vinblastine, resperine, ajmalcine. Here we review the

recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and

characterization of the corresponding enzymes involved in this pathway. Vincristine and vinblastine are used for treatment

of various type of cancer such as Hodgkin’s disease, breast cancer, leukemia etc. Madagascar periwinkle is poisonous if

ingested or smoked. The pharmacognostical aspects of cathranthus roseus alkaloid cover botanical, phytochemical and

analytical data. It has high medicinal value which needs to be explored extensively.

KEYWORD: Catharanthus roseus, Vinblastine, Vincristine, Anticancer, Antidiabetic.

INTRODUCTION

India is a country known for ancient scripts the number

system and invention of zero and Vedas. Medicines in

India are used by about 60 percent of world’s population.

With the scripts in the Atharva Veda, we have evidence of

a traditional use of medicinal plants that is more than 3000

years old. It is estimated that about 80,000 species plants

are utilized in some forms other by the different system of

India medicine. The corroborative and tonic plant generally

known as the rasayana drugs in ayurveda are known to

prevent ageing, increase longevity and offer resistance to

disease by augmenting the immune system.[1] World

health organization (WHO) have been prepared a list of

21000 medicinal important plant one such plant is

Catharanthus roseus (L) It belongs to family Apocynaceae

and a rich source of alkaloid. These are used for various

purposes such as pharmaceuticals, food additives and dyes.

Plant Introduction

CATHARNTHUS is a genus of flowering plants in the

dogbane family, Apocynaceae like genus vinca, they are

commonly known as periwinkles [2] there are eight known

species, and seven are endemic to Madagascar [3]Though

one, CATHARANTHUS ROSEUS is widely naturalized

around the world.[4] Name CATHARANTHUS comes

from the Greek word ‚Pure flower‛[5]

Botanical Description

i. Height: It is an herbaceous plant growing 1m

long[6]

ii. Leaves: The leaves are oval to oblong 2.5 -9cm.

broad, glossy green hairless with a pale midrib

and a short petiols 1-1.8cm long [7]

iii. Flower: The flowers are white to dark pink with a

darker red centre[8]

iv. Fruit: The fruit is a pair of follicles 2-4cm. longand

2mm. broad [9]

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Figure 1: flower of c.roseus

Plant Use- There are following use of c. roses:

i. Used as medicine: In Ayurveda the extracts of its roots and shoots, is used against several disease including

Diabetis, Malaria etc[7]

ii. Used as anticancer: The substance vinblastine and vincristine extracted from the plant are used in treatment of

leukemia, Hodgkin’s lymphoma.[9]

iii. In plant pathology: C. roseus is used in plant pathology as an experimental host for phytoplasmas [11]This is

because it is easy to infect with a large majority of phytoplasmas and also often has very distinctive symptoms such

as phyllody and significant reduced leaf size[12]

Figure 2:different alkaloid of c.roseus

Table 1: Different Alkaloid Produced By C.roseu

PRODUCED BY ALKALOID PROPERTIES

ROOT Ajmalicine Cardio-vascular disease and high blood pressure

Catharanthine Anti-Diabetic properties

Raubasin Pain relieving properties

Reserpine Tranquilizers

Serpentine Cardio-vascular disease and high blood pressure

AERIAL PART

LIKE LEAVES

Vinblastine Anti-Tumour properties

Vincristine Anti-Tumour properties

Vindoline Anti-Tumour properties

Figure 3: General properties of C. Roseus

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CULTIVATION

Culture

Madagascar periwinkle does best in poor, well-drained

soils. Flowering will suffer if soils are too fertile. Pinch

back early in the season to encourage branching and a

fuller plant. Madagascar periwinkle doesn't need

deadheading - the flowers drop off when they finish

blooming.

Light Full sun or partial shade

Moisture Madagascar periwinkle should be watered

moderately during the growing season, but it is relatively

drought resistant once established. In fact, it is unusually

drought resistant for an annual. Madagascar periwinkle is

not at all tolerant of overwatering

Hardiness USDA Zones 9-11. Non-stop summertime

flowers and heat resistance make this rugged plant a good

choice to grow as an annual in cooler Zones.

Propagation Madagascar periwinkle is usually grown

from seed, but also can be rooted from cuttings taken in

spring or summer. It will reseed itself if the soil is

loose.[13]

WARNING

Madagascar periwinkle is poisonous if ingested or smoked.

It has caused poisoning in grazing animals. Even under a

doctor's supervision for cancer treatment, products from

Madagascar periwinkle produce undesirable side

effects.[13]

Phytochemical and Biochemical Properties

Catharanthus roseus is one of the most extensively

investigated medicinal plants, which can produce more

than 130 alkaloids, including the powerful antitumor drugs

vinblastine and vincristine. Here we review the recent

advances in the biosynthetic pathway of terpenoid indole

alkaloids (TIAs) in C. roseus, and the identification and

characterization of the corresponding enzymes involved in

this pathway. Strictosidine is the central intermediate in

the biosynthesis of different TIAs, which is formed by the

condensation of secologanin and tryptamine. Secologanin

is derived from terpenoid (isoprenoid) biosynthetic

pathway, while tryptamine is derived from indole

biosynthetic pathway. Then various specific end products

are produced by different routes during downstream

process. Although many genes and corresponding enzymes

have been characterized in this pathway, our knowledge on

the whole TIA biosynthetic pathway still remains largely

unknown up to date. Full elucidation of TIA biosynthetic

pathway is an important prerequisite to understand the

regulation of the TIA biosynthesis in the medicinal plant

and to produce valuable TIAs by synthetic biological

technology [14]

The Madagascar periwinkle produces a large palette of

Monoterpenoid Indole Alkaloids (MIAs), a class of

complex alkaloids including some of the most valuable

plant natural products with precious therapeutically values.

Evolutionary pressure on one of the hotspots of

biodiversity has obviously turned this endemic Malagasy

plant into an innovative alkaloid engine. Catharanthus is a

unique taxon producing vinblastine and vincristine,

heterodimeric MIAs with complex stereochemistry, and

also manufactures more than 100 different MIAs, some

shared with the Apocynaceae, Loganiaceae and Rubiaceae

members. For over 60years, the quest for these powerful

anticancer drugs has inspired biologists, chemists, and

pharmacists to unravel the chemistry, biochemistry,

therapeutic activity, cell and molecular biology of

Catharanthus roseus. Recently, the "omics" technologies

have fuelled rapid progress in deciphering the last secret of

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strictosidine biosynthesis, the central precursor opening

biosynthetic routes to several thousand MIA compounds.

Dedicated C. roseus transcriptome, proteome and

metabolome databases, comprising organ-, tissue- and cell-

specific libraries, and other phytogenomic resources, were

developed for instance by PhytoMetaSyn, Medicinal Plant

Genomic Resources and SmartCell consortium. Tissue

specific library screening, orthology comparison in species

with or without MIA-biochemical engines, clustering of

gene expression profiles together with various functional

validation strategies, largely contributed to enrich the

toolbox for plant synthetic biology and metabolic

engineering of MIA biosynthesis.[15]

Environmental pressures forced plants to diversify

specialized metabolisms to accumulate noxious molecules

such as alkaloids constituting one of the largest classes of

defense metabolites. Catharanthus roseus produces

monoterpene indole alkaloids via a highly elaborated

biosynthetic pathway whose characterization greatly

progressed with the recent expansion of transcriptomic

resources. The complex architecture of this pathway,

sequentially distributed in at least four cell types and

further compartmentalized into several organelles, involves

partially identified inter-cellular and intra-cellular

translocation events acting as potential key-regulators of

metabolic fluxes. The description of this spatial

organization and the inherent secretion and sequestration

of metabolites not only provide new insight into alkaloid

cell biology and its involvement in plant defense processes

but also present new biotechnological challenges for

synthetic biology [16] Monoterpene indole alkaloids

(MIAs) encompass plant natural products with important

pharmacological relevance. They include the anti-tumoral

MIAs found in Catharanthus roseus and Camptotheca

acuminata.The often low yields of bioactive alkaloids in

plants has prompted research to identify the factors

regulating MIA production. Oxidative stress is a general

response associated with biotic and abiotic stresses leading

to several secondary responses, including elicitation of

MIA production. These changes in secondary metabolism

may take place directly or via second messengers, such as

Ca(2+) and reactive oxygen species (ROS). H2O2 is the

main ROS that participates in MIA biosynthesis. This

review analyzes the links between oxidative stress,

elicitation of bioactive MIA production and their potential

roles in antioxidant defense, as well as exploring the

implications to developing biotechnological strategies

relevant for alkaloid supply.[17] This review looks back on

how the terpenoid indole alkaloid pathway and the

regulatory factors in Catharanthus roseus were identified

and characterized,and how metabolic engineering,

including genetic engineering and metabolic profiling, was

conducted based on the gained knowledge. In addition,

further examination of the terpenoid indole alkaloid

pathway is proposed.[18]

Catharanthus roseus (The Madagaskar Periwinkle) plant is

commercially valued for harbouring more than 130

bioactive terpenoid indole alkaloids (TIAs). Amongst

these, two of the leaf-derived bisindole alkaloids-

vinblastine and vincristine-are widely used in several

anticancer chemotherapies. The great pharmacological

values, low in planta occurrence, unavailability of synthetic

substitutes and exorbitant market cost of these alkaloids

have prompted scientists to understand the basic

architecture and regulation of biosynthesis of these TIAs in

C. roseus plant and its cultured tissues. The knowledge

gathered over a period of 30 years suggests that the TIA

biosynthesis is highly regulated by developmental and

environmental factors and operates through a complex

multi-step enzymatic network. Extensive spatial and

temporal cross talking also occurs at inter- and intracellular

levels in different plant organs during TIA biogenesis. A

close association of indole, methylerythritol phosphate and

secoiridoid monoterpenoid pathways and involvement of at

least four cell types (epidermis, internal phloem-associated

parenchyma, laticifers and idioblasts) and five intracellular

compartments (chloroplast, vacuole, nucleus, endoplasmic

reticulum and cytosol) have been implicated with this

biosynthetic mechanism. Accordingly, the research in this

area is primarily advancing today to address and resolve six

major issues namely: precise localization and expression of

pathway enzymes using modern in situ RNA hybridization

tools, mechanisms of intra- and intercellular trafficking of

pathway intermediates, cloning and functional validation of

genes coding for known or hitherto unknown pathway

enzymes, mechanism of global regulation of the pathway

by transcription factors, control of relative diversion of

metabolite flux at crucial branch points and finally,

strategising the metabolic engineering approaches to

improve the productivity of the desired TIAs in plant or

corresponding cultured tissues. The present literature

update has been compiled to provide a brief overview of

some of the emerging developments in our current

understanding of TIA metabolism in C. roseus [19]

In plants, organ formation and cell elongation require the

constant adjustment of the dynamic and adaptable cell wall

in response to environmental cues as well as internal

regulators, such as light, mechanical stresses, pathogen

attacks, phytohormones, and other signaling molecules.

The molecular mechanisms that perceive these cues and

translate them into cellular responses to maintain integrity

and remodelling of the carbohydrate-rich cell wall for the

coordination of cell growth are still poorly understood. In

the last 3 years, the function of six membrane-localized

receptor-like kinases (RLKs) belonging to the CrRLK1L

family has been linked to the control of cell elongation in

vegetative and reproductive development. Moreover, the

presence of putative carbohydrate-binding domains in the

extracellular domains of these CrRLK1Ls makes this

receptor family an excellent candidate for coordinating cell

growth, cell-cell communication, and constant cell wall

remodeling during the plant life cycle [20] The roll of

receptor like kinases in regulating cell wall function.[21]

The Madagascar periwinkle is a plant species known for its

production of TIAs (terpenoid indole alkaloids), many of

which are pharmaceutically important. Ajmalicine and

serpentine are prescribed for the treatment of hypertension,

whereas the bisindoles vinblastine, vincristine and 3',4'-

anhydrovinblastine are used for their antineoplastic activity

in the treatment of many cancers. However, TIAs are

produced in small yields in C. roseus, which make them

expensive. Cell and metabolic engineering has focused on

increasing flux through the TIA pathway by various means,

including optimization of medium composition, elicitation,

construction of noval culture systems and introduction of

genes encoding specific metabolic enzymes into the C.

roseus genome. The present review will attempt to present

the state-of-the-art of research in this area and provide an

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update on the cell and metabolic engineering of TIAs in C.

roseus. We hope that this will contribute to a better

understanding of the ways in which TIA production can be

achieved in different C. roseus culture systems[22]

Brassinosteroids represents a class of plant hormones.

More than 70 compounds have been isolated from plants.

Currently 42 brassinosteroid metabolites and their

conjugates are known. This review describes the

miscellaneous metabolic pathways of brassinosteroids in

plants. There are some types of metabolic processes

involving brassinosteroids in plants: dehydrogenation,

demethylation, epimerization, esterification, glycosylation,

hydroxylation, side-chain cleavage and sulfonation.

Metabolism of brassinosteroids can be divided into two

categories: i) structural changes to the steroidal skeleton;

and ii) structural changes to the side-chain.[23]

Monoterpene indole alkaloids (MIAs) are a large class of

plant alkaloids with significant pharmacological interest.

The sustained production of MIAs at high yields is an

important goal in biotechnology. Intensive effort has been

expended toward the isolation, cloning, characterization

and transgenic modulation of genes involved in MIA

biosynthesis and in the control of the expression of these

biosynthesis-related genes. At the same time, considerable

progress has been made in the detailed description of the

subcellular-, cellular-, tissue- and organ-specific

expressions of portions of the biosynthetic pathways

leading to the production of MIAs, revealing a complex

picture of the transport of biosynthetic intermediates

among membrane compartments, cells and tissues. The

identification of the particular environmental and

ontogenetic requirements for maximum alkaloid yield in

MIA-producing plants has been useful in improving the

supply of bioactive molecules. The search for new

bioactive MIAs, particularly in tropical and subtropical

regions, is continuously increasing the arsenal for

therapeutic, industrially and agriculturally useful

molecules. In this review we focus on recent progress in

the production of MIAs in transgenic cell cultures and

organs (with emphasis on Catharanthus roseus and

Rauvolfia serpentine alkaloids), advances in the

understanding of in planta spatial-temporal expression of

MIA metabolic pathways, and on the identification of

factors capable of modulating bioactive alkaloid

accumulation in nontransgenic differentiated cultures and

plants (with emphasis on new MIAs from Psychotria

species). The combined use of metabolic engineering and

physiological modulation in transgenic and wild-type

plants, although not fully exploited to date, is likely to

provide the sustainable and rational supply of bioactive

MIAs needed or human wellbeing [24]Advances in the

study on critical steps in the biosynthesis pathway of

Catharanthus alkaloids and the regulation of their

metabolism [25]

Studies on the biosynthesis of sterol side chain in higher

plants. Campesterol [3] and dihydrobrassicasterol [4]

typical C28-sterols in higher plants, are biosynthesized

from a steroidal 24-ene precursor (desmosterol 1) via 24-

methylenecholesterol [2] and 24-methyldesmosterol [5] A

typical plant C29-sterol, sitosterol [6] is produced from 24-

methylenecholesterol via isofucosterol [7] and 24-

ethyldesmosterol [8] The biosynthetic mechanism,

focussing stereochemical features, of these side-chain

transformations has been studied in detail by feeding regio-

and stereoselectively 13C- or 2H-labeled steroidal

substrates to cell cultures of higher plants such as Oryza

sativa, Catharanthus roseus and Morus alba. These studies

allowed correlating the metabolic origin of C-26 and C-27

of the intermediate sterols. It has been established that the

1st methylation leading to 24-methylenecholesterol from

desmosterol involves a Re-face hydrogen migration from

C-24 to C-25 based on unambiguous assignment of the

isopropyl pro-R-Me and pro-S-Me of 24-

methylenecholesterol. The 2nd methylation leading to

isofucosterol was revealed to proceed in a trans-mechanism

in which addition of the methyl group and elimination of

the C-28 hydrogen occur on opposite faces of the original

delta 24(28) plane. The double bond isomerization from

delta 24(28) to delta 24(25) was found to proceed in a syn-

SE2' mechanism with the pro-S-methyl group of

isofucosterol becoming the (E)-methyl of 24-

ethyldesmosterol. Finally, feeding studies of [E-Me-13C]-

and [Z-Me-13C]-24-methyldesmosterols established that an

anti-mode of hydrogen addition is operating in the

conversion of 24-methyldesmosterol to campesterol and

dihydrobrassicasterol. Similar studies established that 24-

ethyldesmosterol is converted to sitosterol in an anti-mode

of hydrogen addition. In addition, the mechanism of sterol

side-chain formation in hairy roots of Ajuga reptans var.

atropurpurea is briefly described [26] Alkaloid

accumulation in Catharanthus roseus suspension

cultures[27]

A significant amount of research has contributed to

characterization of several individual steps in the

biosynthetic pathway of medicinally valuable alkaloids.

However, knowledge of the regulation of these pathways is

still sparse. Using hairy root cultures, we studied the

responses of alkaloid metabolism to environmental

stimulation such as light and elicitation. Through precursor

feeding studies, the putative rate-limiting steps of the

terpenoid pathway in hairy root cultures also have been

examined. Relating this knowledge to specific events at the

molecular level, and the cloning of corresponding genes

are the next key steps in metabolic engineering of the C.

roseus alkaloids.[28] Biosynthesis of steroidal plant

hormones, brassinosteroids, was studied using the cell

culture system of Catharanthus roseus. Feeding labeled

compounds of possible intermediates to the cultured cells,

followed by analyzing the metabolites by gas

chromatography-mass spectrometry disclosed the

pathways from a plant sterol, campesterol, to brassinolide.

There are two pathways, named the early C6-oxidation

pathway and late C6-oxidation pathway, both of which

would be operating in a wide variety of plants. Recent

findings of brassinosteroid-deficient mutants of

Arabidopsis and the garden pea by several groups, and the

possible blocked steps of the mutants in the biosynthetic

pathways are also introduced [29]

Indole alkaloids in Catharanthus roseus have been in focus

because of their medicinal value. These alkaloids consist of

an indole moiety provided by tryptamine and a terpenoid

portion provided by the secologanin. The most important

catharanthus alkaloids are vinblastine (VLB), vincristine

(VCR) and ajmalicine. VLB and VCR are clinically useful

anticancer agents whereas ajmalicine is used for the

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treatment of circulatory diseases. VCR and VLB are the

most expensive because of their low abundance in the

plant, and are formed by the coupling of monomeric indole

alkaloids vindoline and catharanthine, catalysed by

peroxidases. The pathway that lead to monomeric indole

alkaloids involves more than 20 enzymes of which 16

enzymes have been isolated and characterized

biochemically,and only three at the molecular level.The

present state of knowledge on enzymes and genes involved

in indole alkaloid biosynthesis and various aspects of their

regulation has been discussed.[30] Alkaloids of

Catharanthus roseus G.Don.new group of biologically

active compound [31]

Clinical and Pharmacological Properties

Catharanthus roseus is a medicinal plant belonging to the

family Apocynaceae which produces terpenoid indole

alkaloids (TIAs) of high medicinal importance. Indeed, a

number of activities like antidiabetic, bactericide and

antihypertensive are linked to C. roseus. Nevertheless, the

high added value of this plant is based on its enormous

pharmaceutical interest, producing more than 130 TIAs,

some of which exhibit strong pharmacological activities.

The most striking biological activity investigated has been

the antitumour effect of dimeric alkaloids such as

anhydrovinblastine, vinblastine and vincristine which are

already in pre-, clinical or in use. The great

pharmacological importance of these indole alkaloids,

contrasts with the small amounts of them found in this

plant, making their extraction a very expensive process. To

overcome this problem, researches have looked for

alternative sources and strategies to produce them in

higher amounts. In this sense, intensive research on the

biosynthesis of TIAs and the regulation of their pathways

has been developed with the aim to increase by

biotechnological approaches, the production of these high

added value compounds. This review is focused on the

different strategies which improve TIA production, and in

the analysis of the beneficial effects that these compounds

exert on human health.[32]

Catharanthus roseus (L.) known as Madagascar periwinkle

(MP) is a legendary medicinal plant mostly because of

possessing two invaluable antitumor terpenoid indole

alkaloids (TIAs), vincristine and vinblastine. The plant has

also high aesthetic value as an evergreen ornamental that

yields prolific blooms of splendid colors. The plant

possesses yet another unique characteristic as an amiable

experimental host for the maintenance of the smallest

bacteria found on earth, the phytoplasmas and

spiroplasmas, and serves as a model for their study.

Botanical information with respect to synonyms,

vernacular names, cultivars, floral morphology, and

reproduction adds to understanding of the plant while the

geography and ecology of periwinkle illustrate the

organism's ubiquity. Good agronomic practices ensure

generous propagation of healthy plants that serve as a

source of bioactive compounds and multitudinous

horticultural applications. The correlation between genetic

diversity, variants, and TIA production exists. MP is

afflicted with a whole range of diseases that have to be

properly managed. The ethnobotanical significance of MP

is exemplified by its international usage as a traditional

remedy for abundant ailments and not only for cancer.

TIAs are present only in micro quantities in the plant and

are highly poisonous per se rendering a challenge for

researchers to increase yield and reduce toxicity [33]

Vinca alkaloids Vinca alkaloids are a subset of drugs

obtained from the Madagascar periwinkle plant. They are

naturally extracted from the pink periwinkle plant,

Catharanthus roseus G. Don and have a hypoglycemic as

well as cytotoxic effects. They have been used to treat

diabetes, high blood pressure and have been used as

disinfectants. The vinca alkaloids are also important for

being cancer fighters. There are four major vinca alkaloids

in clinical use: Vinblastine (VBL), vinorelbine (VRL),

vincristine (VCR) and vindesine (VDS). VCR, VBL and

VRL have been approved for use in the United States.

Vinflunine is also a new synthetic vinca alkaloid, which

has been approved in Europe for the treatment of second-

line transitional cell carcinoma of the urothelium is being

developed for other malignancies. Vinca alkaloids are the

second-most-used class of cancer drugs and will stay

among the original cancer therapies. Different researches

and studies for new vinca alkaloid applications will be

carried out in this regard [34]

An exploration of the potential mechanisms and

translational potential of five medicinal plants for

applications in Alzheimer's disease (AD) is the most

common type of dementia, and represents a vast

worldwide socio-economic burden, and in the absence of a

current cure, effective therapeutic strategies are still

needed. Cholinergic and cerebral blood flow deficits,

excessive levels of oxidative stress, neuroinflammation and

glutamate excitatory mechanisms are all believed to

contribute to the development and progression of the

disease. Scoparia dulcis, Catharanthus roseus, Sesamum

indicum, Erythrina senegalensis and Vigna unguiculata

represent five plants that have been used as traditional

medicines for the treatment of AD in certain cultures.

Review of the scientific literature was conducted to explore

the properties of these plants that might be beneficial and

explain what would be perceived by many to be largely

anecdotal evidence of their benefit. All plants were found

to possess varying levels of anti-oxidant capability.

Scoparia dulcis was also found to potentiate nerve growth

factor-like effects upon cell lines. Catharanthus roseus

appears to inhibit acetylcholinesterase with relatively high

potency, while Sesamum indicum demonstrated the

strongest antioxidant ability. Comparisons with currently

used plant derived therapeutics illustrate how these plants

may be likely to have some therapeutic benefits in AD.

The evidence presented also highlights how appropriate

dietary supplementation with some of these plants in

various cultural settings might have effects analogous or

complementary to the so-called protective Mediterranean

diet. However, prior to embarking on making any formal

recommendations to this end, further rigorous evaluation is

needed to better elucidate the breadth and potential

toxicological aspects of medicinal properties harbored by

these plants. This would be vital to ensuring a more

informed and safe delivery of preparations of these plants if

they were to be considered as a form of dietary

supplementation and where appropriate, how these might

interact with more formally established therapies in

relation to AD[35]]

The antimicrobial activities of four medicinal plants

Argemona mexicana, Achyranthes aspera, Catharanthus

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roseus, and Syzygium cumini were evaluated against

Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae,

Proteus vulgaris, Bacillus subtilis, Salmonella typhi and

three Aspergillus species. Extracts from Achyranthes

aspera and Catharanthus roseus showed the highest

antimicrobial potential (MIC 0.375-0.750 mg/ml) while

extract from Argemona mexicana and Syzygium cumini,

showed less activity. In disc diffusion assay, only eight out

of twenty extracts showed antimicrobial activity at a

concentration of 25.0 μg/ disc. The GCMS investigation

reveals the existence of 2-bornanone; 1, 2-

benzenedicarboxylic acid, bis (2-methylpropyl) ester;

hexadecanoic acid, methyl ester and hexatriacontane in

water extract fraction of C. roseus. The present research

article provides a review of some medicinal plants

incorporating antimicrobial drugs, together with recent

advances in emerging therapeutics inclinical development

and related patents for exploitation of herbal medicine [36]

Receptor-like kinase complexes in plant innate

immunity.Receptor-like kinases (RLKs) are surface

localized, transmembrane receptors comprising a large

family of well-studied kinases. RLKs signal through their

transmembrane and juxtamembrane domains with the aid

of various interacting partners and downstream

components. The N-terminal extracellular domain defines

ligand specificity, and RLK families are sub-classed

according to this domain. The most studied of these

subfamilies include those with (1) leucine-rich repeat

(LRR) domains, (2) LysM domains (LYM), and (3) the

Catharanthus roseus RLK1-like (CrRLK1L) domain.

These proteins recognize distinct ligands of microbial

origin or ligands derived from intracellular

protein/carbohydrate signals. For example, the pattern-

recognition receptor (PRR) AtFLS2 recognizes flg22 from

flagellin, and the PRR AtEFR recognizes elf18 from

elongation factor (EF-Tu). Upon binding of their cognate

ligands, the aforementioned RLKs activate generic

immune responses termed pattern-triggered immunity

(PTI). RLKs can form complexes with other family

members and engage a variety of intracellular signaling

components and regulatory pathways upon stimulation.

This review focuses on interesting new data about how

these receptors form protein complexes to exert their

function [37]

Micropropagation: a tool for the production of high quality

plant-based medicines. Medicinal plants are the most

important source of life saving drugs for the majority of the

world's population. The biotechnological tools are

important to select, multiply and conserve the critical

genotypes of medicinal plants. Plant tissue culture

techniques offer an integrated approach for the production

of standardized quality phytopharmaceutical through mass-

production of consistent plant material for physiological

characterization and analysis of active ingredients.

Micropropagation protocols for cloning of some medicinal

plants such as Catharanthus roseus (Apocynaceae),

Chlorophytum borivilianum (Liliaceae), Datura metel

(Solanaceae), and Bacopa monnieri (Scrophulariaceae)

have been developed. Regeneration occurred via

organogenesis and embryogenesis in response to auxins

and cytokinins. The integrated approaches of our culture

systems will provide the basis for the future development

of novel, safe, effective, and high-quality products for

consumers [38]

The Catharanthus (or Vinca) alkaloids comprise a group of

about 130 terpenoid indole alkaloids. Vinblastine is now

marketed for more than 40 years as an anticancer drug and

became a true lead compound for drug development. Due

to the pharmaceutical importance and the low content in

the plant of vinblastine and the related alkaloid vincristine,

Catharanthus roseus became one of the best-studied

medicinal plants. Consequently it developed as a model

system for biotechnological studies on plant secondary

metabolism. The aim of this review is to acquaint a broader

audience with the recent progress in this research and with

its exciting perspectives. The pharmacognostical aspects of

the Catharanthus alkaloids cover botanical (including some

historical), phytochemical and analytical data. An up-to-

date view on the biosynthesis of the alkaloids is given. The

pharmacological aspects of these alkaloids and their semi-

synthetic derivatives are only discussed briefly. The

biotechnological part focuses on alternative production

systems for these alkaloids, for example by in vitro culture

of C. roseus cells. Subsequently it will be discussed to

what extent the alkaloid biosynthetic pathway can be

manipulated genetically ("metabolicengineering"), aiming

at higher production levels of the alkaloids. Another

approach is to produce the alkaloids (or their precursors) in

other organisms such as yeast. Despite the availability of

only a limited number of biosynthetic genes, the research

on C. roseus has already led to a broad scientific spin-off. It

is clear that many interesting results can be expected when

more genes become available.[39]

Neurological syndromes linked with the intake of plants

and fungi containing a toxic component (I). Neurotoxic

syndromes caused by the ingestion of plants, seeds and

fruits. A wide range of plants, seeds and fruits used for

nutritional and medicinal purposes can give rise to

neurotoxic symptoms.We review the neurological

pathology associated with the acute or chronic

consumption of plants, seeds and fruits in human beings

and in animals. Of the plants that can trigger acute

neurotoxic syndromes in humans, some of the most

notable include Mandragora officinalis, Datura

stramonium, Conium maculatum (hemlock), Coriaria

myrtifolia (redoul), Ricinus communis, Gloriosa superba,

Catharanthus roseus, Karwinskia humboldtiana and

Podophyllum pelatum. We also survey different

neurological syndromes linked with the ingestion of

vegetable foodstuffs that are rich in cyanogenic glycosides,

Jamaican vomiting sickness caused by Blighia sapida,

Parkinson dementia ALS of Guam island and exposition to

Cycas circinalis, Guadeloupean parkinsonism and

exposition to Annonaceae, konzo caused by ingestion of

wild manioc and neurolathyrism from ingestion of

Lathyrus sativus, the last two being models of motor

neurone disease. Locoism is a chronic disease that

develops in livestock feeding on plants belonging to

Astragalus and Oxytropis sp., Sida carpinifolia and Ipomea

carnea, which are rich in swainsonine, a toxin that inhibits

the enzyme alpha mannosidase and induces a cerebellar

syndrome.The ingestion of neurotoxic seeds, fruits and

plants included in the diet and acute poisoning by certain

plants can give rise to different neurological syndromes,

some of which are irreversible.[40]

JP 15|Volume 1|Issue 1|2015

8

Aryltetralin lignans: chemistry, pharmacology and

biotransformations. Podophyllotoxin derivatives like

etoposide 7a, etophos 7b, and teniposide 7c are used

clinically as potent chemotherapeutic agents for a variety

of tumors including small cell lung carcinoma, testicular

cancer, and malignant lymphoma. These compounds

derived from a series of modifications which converted

podophyllotoxin 1a from an entity that interacted with

tubulin and blocks mitosis to one that induced a block in

late S or early G2 by interacting with topoisomerase II.

Synthetic studies on podophyllotoxin derivatives can be

divided in four general approaches (the oxo-ester route, the

digydroxy acid route, the tandem conjugate addition route

and the Diels-Alder route). Albeit a number of synthetic

sequences afforded products with excellent enantiopurities,

the low overall yields still disqualify synthesis as an

alternative for naturally produced materials. An alternative

route based on the enzyme-catalyzed cyclization of

synthetic intermediates to analogues of the

podophyllotoxin family is being explored. Synthetic

dibenzylbutanolides, which were revealed by biosynthetic

studies to be the precursors of aryltetralin lignans, have

been treated with enzymes derived from cell cultures of

Podophyllum peltatum, Catharanthus roseus, Nicotiana

sylvestris and Cassia didymobotrya. The ciclyzation

process afforded however compounds with a different

stereochemistry in the C ring. The obtainment of a novel

compound with a bynzylidenebenzylbutirolactone

structure still leaves considerable scope for exploring

biotransformations in order to obtain podophyllotoxin

analogues via a combination of synthetic chemistry and

biotechnological methods.[41]

Clinical pharmacokinetics of vinorelbine.Vinorelbine (5'-

noranhydrovinblastine) is a recently developed

semisynthetic anticancer drug which belongs to the

Catharanthus alkaloid family. Its mechanism of action is

only partially known but it is assumed that it acts, like

vinblastine and vincristine, as an antimicrotubule agent

arresting cell division in mitosis. Clinica lly, vinorelbine

has mainly shown activity in the treatment of advanced

non-small-cell lung cancer and the treatment of metastatic

breast cancer. Early pharmacokinetic data were obtained

with radioactive assays (radio-immunoassay or 3H-labelled

vinorelbine), then with more selective high performance

liquid chromatographic techniques. Vinorelbine is usually

administered intravenously but there has also been some

experimentation with an oral formulation. The

bioavailability of a liquid filled gelatin capsule ranges

between 12 and 59% with a mean value of 27% [standard

deviation (SD) 12%]. Vinorelbine is rapidly absorbed with

peak serum concentration reached within 2 hours. In vitro,

vinorelbine is mainly distributed into the blood cells,

especially platelets (78%) and lymphocytes (4.8%) The

unbound blood fraction is around 2%. In lung tissue

vinorelbine concentrations are much higher than in serum,

by up to 300-fold 3 hours after administration. Little is

known about the biotransformation of vinorelbine.

Desacetylvinorelbine is considered to be a minor

metabolite and is only found in urine fractions,

representing 0.25% of the injected dose. Urinary excretion

of vinorelbine is low, accounting for less than 20% of the

dose. Faecal elimination has been demonstrated in

2patients who were administered 3H-labelled vinorelbine;

the amount of radioactivity recovered in the faeces was

33.9 and 58.4% for the 2 patients, respectively. The

pharmacokinetic profile of vinorelbine is often described as

a 3-compartment model characterized by a long terminal

half-life (t1/2) that varies between 20 and 40 hours and a

large apparent volume of distribution (Vd) of around 70

L/kg. Systemic clearance ranges between 72.54 and 89.46

L/h (1209 and 1491 ml/min) when determined by high

performance liquid chromatography and is higher than that

reported by radioimmunoassay [46.2 L/h (770 ml/min)].

This could be due to the greater specificity of the

chromatographic method. Vinorelbine has been

administered by continuous intravenous infusion over 4

days. Steady-state was reached and the concentrations

obtained were above the in vitro IC50 (concentration of

drug causing 50% inhibition). The effect of liver disease on

vinorelbine pharmacokinetics has been studied in patients

with breast cancer. Patients with massive secondary liver

disease had a lower systemic clearance than those who

have no liver disease or a lesser invasion. In children,

vinorelbine seems to display a shorter t1/2 (14.7 hours)

than that found in adults. In addition, the systemic

clearance is highly variable [from 12 to 93.96 L/h/m2

(200to 1566 ml/min/m2)]. Vinorelbine is often co-

administered with cisplatin in the treatment of advanced

non-small-cell lung cancer. The disposition of the alkaloid

is not altered by concurrent administration of cisplatin[42]

Pharmacologyof Catharanthus alkaloids.Catharanthus

alkaloids are antitumoral drugs widely used in the

treatment of malignant diseases. This review summarizes

different aspects of their pharmacology (mechanism of

action, resistance, clinical pharmacokinetics) as well as

information on their uses in the clinical setting.[43]

Cytochrome P-450 in plant/insect interactions: geraniol 10-

hydroxylase and the biosynthesis of iridoid

monoterpenoids. The interactions between plant secondary

metabolites (particularly monoterpenes) and insects are

discussed. Such metabolites are likely to have influenced

the evolution of cyt P450-linked detoxification systems in

animals, through animal/plant coevolution. The

biosynthesis of many classes of plant secondary

metabolites involves cyt P450 enzymes.Of these, one of

the best characterised is the geraniol/nerol 10-hydroxylase

which catalyses a key step in the biosynthesis of the iridoid

class of plant terpenes. It would appear that these

monoterpenoids are synthesised (via cyt P450

hydroxylation) from different precursors in different plant

species, namely geraniol, its isomer nerol, or the related

monoterpenoid, citronellol. We show that cyt P450 from

the plants Catharanthus roseus and Nepeta racemosa are

capable of hydroxylating geraniol, nerol and citronellol,

and thus do not impose precursor specificity on iridoid

biosynthesis in plants[44]

The pharmacology of extinction.It is impossible to predict

what compounds of pharmacological interest may be

present in an unexamined species. The extinction of such

species may result, therefore, in the loss of therapeutically

significant compounds. The fact that science will never

know what has been lost does not lessen the significance of

the loss. A number of species are discussed to exemplify

the potential loss. Ginkgo biloba is an ancient plant,

apparently saved from a natural extinction by human

intervention. From this tree, the ginkgolides have been

isolated. These are potent inhibitors of platelet activating

factor and hold promise in the treatment of cerebral

ischemia and brain edema. Two species, the tree Taxus

JP 15|Volume 1|Issue 1|2015

9

brevifolia and the leech Hirudo medicinalis, are threatened

as a result of human activity. Both have recently yielded

complex compounds of therapeutic importance.The

antitumor agent, taxol, is obtained from T. brevifolia and

the thrombin inhibitor, hirudin, is found in H.medicinalis.

Catharanthus roseus, source of the anticancer

agentsvincristine and vinblastine, although not threatened,

derives from a largely unexamined but severely stressed

ecosystem of some 5000 plant species. In other examples,

ethnobotanical knowledge of certain plants may be lost

while the species survive, as exemplified by the

suppression of the Aztec ethnobotany of Mesoamerica by

the invading Spanish. Finally, the fallacy of the 'snail darter

syndrome', where species may be viewed as too

insignificant to worry about, is exposed by consideration of

the pharmacological activities of a sea hare (ashell-less

marine mollusc) and various leeches.[45]

The dimeric Vinca alkaloids represent a group of important

anti-tumor compounds whose intracellular target is tubulin,

the protein monomer of microtubules. In this review data

on the binding of these drugs to tubulin and microtubules

in vitro are examined.The simplest model which fits the

binding data is one in which there is one intrinsic site

which is linked to the self-association process. Effects of

solution variables on the binding and self-association

explain the wide variation of reported apparent binding

constants for Vinca alkaloids to tubulin. The Vinca drugs

also bind to microtubules via a low number of sites at the

ends of microtubules with apparent high affinity and which

are involved in the inhibition of tubulin dimer addition to

the microtubule ends, and to sites along the microtubule

wall with apparent low affinity which are involved in the

disruption of the microtubules into spiraled protofilaments.

This review also compares available binding data for

different natural and semi-synthetic Vinca alkaloids.[46]

Anticancer Properties

Many anticancer drugs are obtained from natural sources.

Nature produces a variety of toxic compounds, which are

often used as anticancer drugs. Up to now, there are at

least 120 species of poisonous botanicals, animals and

minerals,of which more than half have been found to

possess significant anticancer properties. In spite of their

clinical toxicity, they exhibit pharmacological effects and

have been used as important traditional Chinese medicines

for the different stages of cancer. The article reviews many

structures such as alkaloids of Camptotheca acuminata,

Catharanthus roseus and Cephalotaxus fortunei, lignans of

Dysosma versipellis and Podophyllum emodi, ketones of

Garcinia hanburyi, terpenoids of Mylabris and Ginkgo

biloba, diterpenoids of Tripterygium wilfordii, Euphorbia

fischeriana, Euphorbia lathyris, Euphorbia kansui, Daphne

genkwa, Pseudolarix kaempferi and Brucea javanica,

triterpenoids of Melia toosendan, steroids of Periploca

sepium, Paris polyphylla and Venenum Bufonis, and

arsenic compounds including Arsenicum and Realgar. By

comparing their related phytochemistry, toxic effects and

the recent advances in understanding the mechanisms of

action, this review puts forward some ideals and examples

about how to increase antitumour activity and/or reduce

the side effects experienced with Chinese medicine.[47]

Vincristine is a dimer-indo-alkaloid which is extracted

from the leaves of Catharanthus roseus. It is effective to

treat acute lymphocytic cell leukemia, Hodgkin disease

and non-Hodgkin disease clinically.But the severe side

effects, such as neurotoxic and tissue damage, limit its

application. In this paper, we summarize physical,

chemical, pharmacological and pharmacokinetical

properties of VCR and advances in decreasing its side

effects. In clinic, association with other medication is

adopted.In pharmaceutics, people adopt some new

methods and technology such as conjugation with the

antibody, encapsulation in liposomes or controlled release

films.[48]The IBOGA alkaloids and their role as precursors

of antineoplasticbisindole Catharanthus alkaloids[49]

Interactions of antimitotic peptides and depsipeptides with

tubulin Tubulin is the target for an ever increasing number

of structurally unusual peptides and depsipeptides isolated

from a wide range of organisms. Since tubulin is the

subunit protein of microtubules, the compounds are usually

potently toxic to mammalian cells. Without

exception,these (depsi)peptides disrupt cellular

microtubules and prevent spindle formation. This causes

cells to accumulate at the G2/M phase of the cell cycle

through inhibition of mitosis. In biochemical assays, the

compounds inhibit microtubule assembly from tubulin and

suppress microtubule dynamics at low concentrations.

Most of the (depsi) peptides inhibit the binding of

Catharanthus alkaloids to tubulin in a noncompetitive

manner,GTP hydrolysis by tubulin, and nucleotide

turnover at the exchangeable GTP site on beta-tubulin. In

general, the (depsi) peptides induce the formation of

tubulin oligomers of aberrant morphology. In all cases

tubulin rings appear to be formed, but these rings differ in

diameter, depending on the (depsi) peptide present during

their formation.[50]

Natural products of plant origin as anticancer

agents.Natural products have been used as effective

remedies for the treatment of various ailments. Numerous

plant products in the form of decoction, tincture, tablets

and capsules have been clinically used for the treatment of

different kinds of cancer. This review covers some of the

important plants with clinically proven anticancer activity,

including Catharanthus roseus, Podophyllum peltatum,

Taxus brevifolia, Camptothecin acuminata, Cephalotaxus

harringtonia, Viscum album, Onchrosia elliptica, Annona

bullata, Asmina triloba and Rhizoma zedoariae. Synthetic

analogues in some cases have also been prepared to

improve the efficacy and decrease the side effects of parent

compounds. The modes of action of clinically used drugs

are also delineated.[51]

In folklore medicine,extracts of the leaves of the

subtropical plant Catharanthus roseus (L.) G.Don

(sometimes known as Madagascar periwinkle) were

reputed to be useful in the treatment of diabetes. This

review describes how attempts to verify the antidiabetic

properties of the extracts led instead to the discovery and

isolation of two complex indole alkaloids, vinblastine and

vincristine, which are used in the clinical treatment of a

variety of cancers. The two alkaloids, although structurally

almost identical, nevertheless differ markedly in the type of

tumors that they affect and in their toxic properties. These

and related alkaloids have been the subject of many

JP 15|Volume 1|Issue 1|2015

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pharmacological and biochemical investigations both in

vivo and in vitro in the search for improved cancer

treatments. A model system used in these studies, a

transplantable lymphoma in Noble strain rats designated

Nb2 node, has serendipitously led to the development of a

highly sensitive and specific bioassay for lactogenic

hormones[52]

Genetic and Molecular Analysis

In plants, receptor-like kinases regulate many processes

during reproductive and vegetative development. The

Arabidopsis subfamily of Catharanthus roseus RLK1-like

kinases (CrRLK1Ls) comprises 17 members with a

putative extracellular carbohydrate-binding malectin-like

domain. Only little is known about the functions of these

proteins, although mutant analyses revealed a role during

cell elongation, polarized growth, and fertilization.

However, the molecular nature ofthe underlying signal

transduction cascades remains largely unknown. CrRLK1L

proteins are also involved in biotic and abiotic stress

responses. It is likely that carbohydrate-rich ligands

transmit a signal, which could originate from cell wall

components, an arriving pollen tube, or a pathogen attack.

Thus, post-translational modifications could be crucial for

CrRLK1L signal transduction and ligand binding [53]

This review focuses on the published data regarding the

molecular determinants (enzymes, transporters, orphan

nuclear receptors) of Catharanthus (vinca) alkaloids

pharmacokinetics in humans. The clinical impact of these

determinants (drug disposition, drug-drug interactions) is

also discussed [54]

Transcription factors: tools to engineer the production of

pharmacologically active plant metabolites. Plants produce

a variety of secondary metabolites, some of which are used

as pharmaceuticals or are health promoting as food

components. Recent genetic studies on the flavonoid

biosynthetic pathway show that transcription factors are

efficient new molecular tools for plant metabolic

engineering to increase the production of valuable

compounds. The use of specific transcription factors would

avoid the time-consuming step of acquiring knowledge

about all enzymatic steps of a poorly characterized

biosynthetic pathway. Although genetic approaches are

difficult for most plant species, promoter studies of single-

pathway genes and T-DNA activation tagging are feasible

alternative approaches for isolating transcription factors, as

illustrated for terpenoid indole alkaloid biosynthesis in

Catharanthus roseus [55]

Metabolism of the Catharanthus alkaloids from

Streptomyces griseus to monoamine oxidase B. More than

three decades after their discovery and implementation in

medicine, essentially nothing is known about the

metabolism or the implications of metabolism in

mechanism of action or toxicity of the Catharanthus

alkaloids.The frustrating paucity of information about

pathways of metabolism has limited a major source of

structure-activity relationship information and has blocked

a critical avenue necessary for the logical development of

new and more useful Catharanthus alkaloids. Microbial

transformations, peroxidases, copper oxidases, mouse and

rat cytochrome P-450 systems, and mouse brain and

bovine liver monoamine oxidase (MAO) preparations have

been explored in the study of Catharanthus alkaloid

metabolism. In this report, we present results which have

clarified the involvement of enzymatic and chemically

catalyzed one-electron oxidations that yield nitrogen-

centered cation radicals, iminium, and carbinolamine

intermediates, all of which explain how new carbon-carbon

and carbon-oxygen bonds form, or break and rearrange.

The dimeric Catharanthus alkaloids are recalcitrant to

oxidations catalyzed by monoamine oxidases and to both

normal and induced P-450 rat microsomal preparations.

However, the Catharanthus alkaloids appear to be selective

reversible inhibitors of MAO-B. Chemical and biochemical

aspects of the metabolic transformations of dimeric

Catharanthus alkaloids are reviewed together with the

implications of our findings[56]

Strategies for the genetic manipulation of alkaloid

producing pathways in plants. Increasingly as a result of

recent biochemical work, there exists a realistic possibility

of taking a molecular genetic approach to the manipulation

of alkaloid-producing pathways in plant tissue cultures. In

the pathways forming indole alkaloids in C.roseus, tropane

alkaloids in Datura and Hyoscyamus species, and nicotine

in Nicotiana species, recent studies have identified a

number of key enzymes and at least some of the factors

that regulate their levels of activity. Such knowledge

contributes the basis upon which it has become feasible to

design a strategy by which the flux in these pathways may

be enhanced at the genomic level. This review presents a

summary of the state-of-the-art pertaining to these

pathways and discusses the strategy to be adopted for a

molecular approach to their manipulation, together with

some of the pitfalls that may arise when trying to alter their

natural regulation.[57]

Antidiabetic Properties

Useful ethnophytomedicinal recipes of angiosperms used

against diabetes in South East AsianCountries(India,

Pakistan & Sri Lanka). This paper is based on data

recorded from various literatures pertaining to

ethnophytomedicinal recipes used against diabetes in

South East Asia (India,Pakistan and Srilanka). Traditional

plant treatments have been used throughout the world for

the therapy of diabetes mellitus. In total 419 useful

phytorecipes of 270 plant species belonging to 74

Angiospermic families were collected. From the review it

was revealed that plants showing hypoglycemic potential

mainly belong to the families, Cucurbitaceae (16 spp.),

Euphorbiaceae (15 spp.), Caesalpiniaceae and

Papilionaceae (13 spp. each), Moraceae (11 spp.),

Acanthaceae (10 spp.), Mimosaceae (09 spp.), Asteraceae,

Malvaceae and Poaceae (08 spp. each), Hippocrateaceae,

Rutaceae and Zingiberaceae (07 spp. each), Apocynaceae,

Asclepiadaceae and Verbenaceae (06 spp. each), Apiaceae,

Convolvulaceae, Lamiaceae, Myrtaceae, Solanaceae (05

spp.each). The most active plants are Syzigium cumini (14

recipes), Phyllanthus emblica (09 recipes), Centella

asiatica and Momordica charantia (08 recipes each),

Azadirachta indica (07 recipes), Aegle marmelos,

Catharanthus roseus, Ficus benghalensis, Ficus racemosa,

Gymnema sylvestre (06 recipes each), Allium cepa, A.

sativum, Andrographis paniculata, Curcuma longa (05

recipes each), Citrullus colocynthis, Justicia adhatoda,

Nelumbo nucifera, Tinospora cordifolia, Trigonella

foenum-graecum, Ziziphus mauritiana and Wattakaka

JP 15|Volume 1|Issue 1|2015

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volubilis (4 recipes each). These traditional recipes include

extracts, leaves, powders, flour, seeds, vegetables, fruits

and herbal mixtures. Data inventory consists of botanical

name, recipe, vernacular name, English name. Some of the

plants of the above data with experimentally confirmed

antidiabetic properties have also been recorded. More

investigations must be carried out to evaluate the

mechanism of action of diabetic medicinal plants. Toxicity

of these plants should also be explained. Scientific

validation of these recipes may help in discovering new

drugs from these medicinal plants for diabetes.[58]

Medicinal plants used for treatment of diabetes by the

Marakh sect of the Garo tribe living in Mymensingh

district, Bangladesh. Diabetes mellitus is an

endocrinological disorder arising from insulin deficiency or

due to ineffectiveness of the insulin produced by the body.

This results in high blood glucose and with time, to

neurological, cardiovascular, retinal and renal

complications. It is a debilitating disease and affects the

population of every country of the world. Around 200

million people of the world suffer from this disease and this

figure is projected to rise to 300 million in the coming

years. The disease cannot be cured with allopathic

medicine as the drugs used do not restore normal glucose

homeostasis and moreover have side-effects. On the other

hand, traditional medicinal practitioners of various

countries claim to cure diabetes or at least alleviate the

major symptoms and progression of this disease through

administration of medicinal plants. The Garos are an

indigenous community of Bangladesh, who still follow

their traditional medicinal practices. Their traditional

medicinal formulations contain a number of plants, which

they claim to be active antidiabetic agents. Since

observation of indigenous practices have led to discovery

of many modern drugs, it was the objective of the present

study to conduct a survey among the Marakh sect of the

Garos residing in Mymensingh district of Bangladesh to

find out the medicinal plants that they use for treatment of

diabetes. It was found that the tribal practitioners of the

Marakh sect of the Garos use twelve medicinal plants for

treatment of diabetes. These plants were Lannea

coromandelica, Alstonia scholaris, , Enhydra fluctuans,

Terminalia chebula, Coccinia grandis, Momordica

charantia, Cuscuta reflexa, Phyllanthus emblica, Syzygium

aqueum, Drynaria quercifolia, and Clerodendrum

viscosum. A review of the scientific literature

demonstrated that almost all the plants used by the Garo

tribal practitioners have reported antidiabetic and/or

antioxidant properties and have enormous potential for

possible development of new and efficacious antidiabetic

drugs.[59]

CONCLUSION

Catharunthus roseus is one of the best studied medicinal

plants. Most recently, extract from periwinkle have been

shown to be effective in treatment of diabetes, high blood

pressure, asthma, constipation, skin cancer, hodgkin’s

disease. Cathranthus roseus in the mid 20th

century after

learning of its use as diabetes treatment in the Caribbean

and Asia. Further Study need to be exploring its anti-tumor

and ant-diabetic effects. In this article have assembled

almost all information related to different research activity

of plant. Same types of reviews have been published on

Tribulus terrestris [60] Oxalis corniculata [61] Solanum

nigrum [62] Cuscuta reflexa [63]], Acorus calamus [64] and

Simarouba Glauca-An oil Yielding Plan [65]This became

popular articles for further investigations on particular

medicinal herbs.

This review will help to researchers & scholars to go deep

in this area as plant indicate vast range of phytochemical

related to origin so it can be suggested the further work can

be done on Catharanthus roseus which is collected from

different season and agro climatic zone. Definitely it is

assumed that research will be able to find out more suitable

and specific drug plant having particular activity in specific

season. Some scientist needs this data and concepts to re-

research on the present scientific plant. It can really

contribute to medical and pharmaceutical practices. There

are still many more activities waiting for screening the

drug from Cathranthus roseus.

ACKNOWLEDGEMENT

We take this opportunity to acknowledge my sincere

thanks to our respected Dr. B. K. Tyagi, Executive

Director, Shri Ram Group of Colleges Muzaffarnagar,

Uttar Pradesh, India, for providing necessary facilities and

tools to carry out the research project work for Post

graduate students of M.Sc. Biotechnology.

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