review of litrature - shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/8127/10/10_chapter...

Chapter – II

REVIEW OF LITRATURE

Basic information about the plant Ricinus communis

Review of phytochemical studies on Ricinus communis

Review of pharmacological studies on Ricinus communis

Review of Literature

17

Basic information about the plant Ricinus communis

Plant introduction

Ricinus communis

Botanical name: Ricinus communis

Family : Euphorbiaceae

Synonym : Ricinus oil

Vernacular names

India : Tamil - Amanakku

Hindi - Arandi

Sanskrit - Eranda

Kannada - Haralenne

Marathi - Erand

Telugu - Aavadam

Malayalam - Aavanakku

Bangla - Erando

Brazil : Carrapateriro, mamona

Ethiopia : Gulo

Korean : Bibeo

Mexico : Higuerilla

Taxonomical Classification

Kingdom : Plantae

Phylum : Magnoliophyta

Class : Magnoliopsida

Order : Malpighiales

Family : Euphorbiaceae

Subfamily : Acalyphoideae

Tribe : Acalypheae

Subtribe : Ricininae

Genus : Ricinus

Species : Ricinus communis


18

Geographical Distribution

The essential constituent of the seeds of the Ricinus communis is

castor oil. Global castor seed (Ricinus communis) production is around I

million tons per year. Leading producing areas are India (with over 60%

of the global yield), China, Brazil, Eastern Africa and Ethiopia. It is wide

spread throughout tropical regions51

.

Description

Although monotypic, the castor oil plant can vary greatly in its

growth habits and appearance depending upon the climatic, Geographical

conditions. It is a fast- growing, suckering perennial shrub which can

reach the size of a small tree (around 12 meters /39feet).

Fig Ia : Ricinus communis Leaves

Fig Ib : Ricinus communis seeds


19

Leaves - The glossy leaf is 15-45 centimeters in length, long -

stalked, alternate and palmate with 5-12 deep lobes with coarsely toothed

segments. Their colour varies from dark green, sometimes with a reddish

tinge, to dark reddish purple or bronze. The stems (and the spherical,

spiny seed pods) also vary in pigmentation. The pods are more shown

than the flowers (Plate- 1a).

Flowers - The flowers borne in terminal panicle - like

inflorescences of green monoecious flowers without petals. The male

flowers are yellowish- green with prominent creamy stamens and are

carried in ovoid spikes up to 15 centimeters long; the female flowers, born

at the tips of the spikes, have prominent red stigmas52

(Fig - 1a).

Fruits / seeds- the fruit is a spiny, greenish (to reddish purple)

capsule containing large, oval, shiny, bean-like, highly poisonous seed

with variable brownish mottling. Castor seeds have a warty appendage

called the caruncle, which is a type of elaiosome. The caruncle promotes

the dispersal of the seed by ants (myrmecochory) (Fig - 1b).

Historical usage

The use of castor bean oil in India has been documented since

2000 BC for lighting lamps and in local medicine as a laxative, purgative,

and cathartic in Unani, Ayurvedic and other ethnomedical systems.

Traditional Ayurvedic medicine considers castor oil the king of medicines

for curing arthritic diseases.


20

REVIEW OF PHYTOCHEMICAL STUDIES ON RICINUS COMMUNIS

Cornelia et al identified homologous very long-chain 1, 3-alkanediols and

3-hydroxyaldehydes in leaf cuticular waxes of Ricinus communis. Surface

extracts from primary leaves of castor bean were found to contain 1.8ug

2cm of cuticular waxes. The mixture comprised alkanes, primary

alcohols, aldehydes, fatty acids and triterpenoids. Besides a series of n-

alkane-1, 3-diols was detected, with chain lengths ranging from to

, a strong predominance of even numbered homologs, and a maximum

for hexacosane-1,3-diol. Seven other compounds were assigned to a novel

class of wax constituents. Both classes of compounds are biosynthetically

related53

.

Kang et al identified various alkaloids and flavonoids in Ricinus

communis leaves. The dried leaves of Ricinus communis afforded two

alkaloids, ricinine and N-demethylricinine and five flavonol glycosides:

kaempferol -3-0- -D-xylopyranoside, kaempferol-3-0- -D-

glucopyranoside, quercetin-3-0- -D-xylopyranoside, quercetin-3-0- -

D- glucopyranoside, kaempferol-3-0- -rutinoside and quercetin -3-0-

-rutinoside. The structures of these compounds were determined through

spectroscopic analysis, chemical correlation and chemical degradation

studies. The flavonoids from this plant were mostly common flavonol-3-

glycosides and the isolates were pairs of xylosides, glucosides and

rutinosides of kaempferol and quercetin54

.

22C

28C


21

Marta Amelia Vattuone et al studied the localization of invertase

activities in Ricinus communis leaves. Leaf tissue from Ricinus communis

possesses cell wall and soluble invertases. These activities may be

distinguished on the basis of their optimum pH and Michaelis constant

(Km) and the action of various inhibitors. Ca 84% of the soluble invertase

was found in vacuolar preparations55

.

Lee et al studied ricinine metabolism and translocation in Ricinus

communis. A new metabolite of ricinine was conclusively identified as 0-

demethylricinine and its interconversion with ricinine in senescent and

green castor plant leaves was demonstrated. Ricinine-3, 5-14

C

administrered in the yellow leaves was translocated to healthy parts of the

plant, especially the growing apex . This finding indicated that

translocation of ricinine may be a process performed by the plants in

order to reutilize the alkaloids from the leaves which are being prepared

for abscission56

.

Pradeep Pratap Singh et al carried out an activity-guided isolation and

purification process to identify the DPPH (1, 1-diphenyl-2-

picrylhydrazyl) free radical scavenging components of the plant Ricinus

communis. Dry leaves of Ricinus communis were extracted with different

solvents and tested for their antioxidant activity and was subjected to

column chromatography over silica gel. Gallic acid, quercetin, gentisic

acid, rutin, epicatechin and ellagic acid were isolated as active

components and characterised by different spectroscopic techniques57

.


22

Kam et al identified the presence of voacangine, voacristine, voacristine-

7-hydroxyindolenine, apparicine, 19-epi-voacristine, conophylline and

conophyllidine. The structures of the dimeric alkaloids were established

by spectral methods and subsequently confirmed by X-ray methods58

.

Henriques et al isolated a new bisindole alkaloid, 19, 20-

dihydroervahanine A from the stems of Ervatamia coranaria together

with five known alkaloids: coronaridine, heyneanine, voacristine,

voacamine, descarbomethoxy voacamine and five phenolic acids: vanillic,

gentisic, syringic, 4-hydroxybenzoic and salicylic acid59

.

Sharma et al isolated a new indole alkaloid 19S-heyneanine

hydroxyindolenine from the whole plant of Ervatamia coronaria. The

acidic and weakly basic fractions of the MeoH extract of the whole plant

contained the terpenoids lupeol, lupeol acetate, -amyrin acetate,-

sitosterol, -sitosterol--D-glucoside and ursolic acid. The basic fraction

contained (-)-19S-heyneanine, voacristine, 3-oxo-coronaridine etc. The

compounds were identified by comparison of their spectral data with

those reported in the literature60

.

PHARMACOLOGICAL REVIEW ON RICINUS COMMUNIS

Vera Coopman et al studied the suicidal death after injection of a castor

bean extract (Ricinus communis). A case report was presented of a 49-

year - old man who committed suicide by intravenous and subcutaneous

injection of a castor bean extract. The patient was admitted in the

emergency department after 24 hours with a history of nausea, vomiting,


23

diarrhea, dyspnoea, vertigo and muscular pain. Despite symptomatic and

supportive intensive care, the man died 9 hours after admission due to

multiorgan failure. Exposure to the castor bean extract was confirmed by

identification of the biomarker ricinine in blood, urine and vitreous humor

using solid phase extraction and liquid chromatography tandem mass

spectrometry. It is the first time that ricine had been identified in vitreous

humor in a case of castor bean poisoning. Based on the clinical symptoms

and the results of the toxicological analysis, it was concluded that death

was caused by intoxication with plant toxins originated from Ricinus

communis61

.

Pamela Mouser et al studied the effects of ingestion of castor bean in a

puppy. Ingestion of masticated seeds resulted in high morbidity, with

vomiting and watery to hemorrhagic diarrhea. The prognosis varied with

the number of seeds ingested, the degree of mastication, individual

susceptibility and the delay in treatment. Despite supportive therapy, the

puppy died several hours after presentation for acute vomiting, diarrhea

and lethargy. Histopathologic findings included superficial necrotizing

enteritis of jejunum and occasional, random foci of coagulative necrosis

in the liver. Ricin toxicosis was confirmed by liquid chromatography/

mass spectrometry using Ricinine as a marker62

.

Stephanie et al studied the cytotoxic properties of the leaves of Ricinus

communis. A volatile extract was obtained from Ricinus communis leaves

by standard hydro distillation and subsequent extraction of the cohobated

water in chloroform. GC-MS identified three monoterpenoids: 1, 8-


24

cineole, camphor and -pinene, and a sesquiterpenoid : -caryophyllene,

as the main constituents. The leaf extract was cytotoxic to several human

tumor cell lines in a dose-dependent fashion. Apoptosis was shown to be

induced in SK-MEL-28 human melanoma cells. Translocation of

phosphatidyl serine to the cell membrane‟s external surface and loss of

mitochondrial membrane potential were also detected63

.

Pingale et al used the powder of Ricinus communis leaves against

hepatosuppression induced by carbon tertachloride. The results were

documented by examination of blood and tissue biochemical marker

enzymes like SGOT, SGPT, alkaline phosphatase etc. Silymarin was used

as a reference standard for comparison. It was found that Ricinus

communis had high potential in healing liver parenchyma and

regeneration of liver cells. It showed best ability to protect liver and may

act in humans even as potent liver tonic due to the presence of large

number of antioxidants64

.

Jose et al investigated the effects of demineralized bone matrix and a

Ricinus communis polymer on bone regeneration histologically in rabbits.

Two surgical bone defects were created in rabbit calvaria, one on the right

and the other on the left side of the parietal suture. The experimental

defects were treated with bovine demineralized bone matrix, human

demineralized bone matrix and polyurethane resin derived from Ricinus

communis oil in three groups of rabbits respectively. Histological analysis

revealed that in all groups bone regeneration increased with time.


25

Polyurethane resorbed more slowly and demonstrated considerably better

results than the demineralized bone matrices65

.

Makonnen et al studied the anti fertility activity of Ricinus communis

seeds in female guinea pigs. The seed extract was found to possess anti

implantation and abortificient effects. It was also observed that the seed

extract prolonged the oestrus cycle of guinea pigs. The dioestrus phase

was significantly prolonged as well. After stopping the administration of

the extract, the normal dioestrus phase and oestrus cycle started to

resume. The seed extract also reduced the weight of the uterus without

affecting that of the ovaries significantly. The antifertility effect of

Ricinus communis in female guinea pigs might be extrapolated to human

beings66

.

Anete et al studied the pharmacological evaluation of ricinine, a central

nervous system stimulant isolated from Ricinus communis in mice. The

extract of the pericarp of castor bean when administered to mice, the

animals became exophthalmic, presented tremors and clonic seizures and

died a few minutes after receiving larger doses of the extract. At lower

doses, the extract improved memory consolidation and showed some

neuroleptic-like properties, such as a decrease in exploratory behavior and

catalepsy. The memory-improving effect and the seizure-eliciting

properties were also observed with the administration of ricinine, a neutral

alkaloid isolated from the extract. However, the neuroleptics like

properties of the extract were not observed with ricinine67

.


26

Visen et al studied the hepatoprotective activity of Ricinus communis

leaves in albino rats. An ethanol extract of the leaves showed significant

protection against galactosamine-induced hepatic damage. It also showed

dose-dependent choleretic and anticholestatic activity as judged by

hepatocytes isolated from paracetamol-treated rats. On fractionation of the

alcohol extract, maximum activity was localised in the butanol fraction.

Subsequent chromatographic fractionation and testing in the

galactosamine model led to the isolation of two active fractions which in

turn yielded two important compounds: ricinine and N-demethyl -ricinine.

N-demethyl-ricinine was found to be more active relatively68

.

Nennesmo et al investigated the effects of retrograde axonal transport of

Ricinus communis agglutinin I (RCAI) on neuroma formation. The lectin

RCAI was topically applied to transected mouse sciatic nerve or to

neuromas formed 2 months after a nerve transaction. Fluorochrome-

labeled ricin was transferred to the corresponding dorsal root ganglia

where it accumulated selectively in the nerve cells, apparently as a

consequence of retrograde axonal transport. The ricin caused an almost

total loss of the dorsal root ganglionic neurons and, consequently, could

prevent formation of neuromas or eliminate an already existing neuroma.

The hybrid toxin wheat germ agglutinin-ricin -A chain caused no apparent

increased sensitivity of neuronal destruction. This method to eliminate

neuromas by selectively destroying sensory neurons may provide a means

to study pain mechanisms in neuromas69

.


27

Natu et al studied the protective effect of Ricinus communis leaves in

experimental liver injury caused by carbon tetrachloride in albino rats.

They reported the pharmacological effects of the whole leaves, cold

aqueous extract and a glycoside extracted from the leaves. The whole

leaves provided protection against liver necrosis as well as changes

induced by while the cold aqueous extract provided protection

only against fatty changes. The glycoside protected the liver from cell

necrosis. Ricinus communis leaves had significant parasympathetic

activity and parasympathetic predominance can be expected to cause an

increase in blood supply to the liver and protection against hepatotoxic

agents70

.

Jonathan David et al investigated the inflammatory gene expression in

response to sub-lethal ricin exposure in mice. The toxin ricin had been

shown to cause inflammatory lung damage, leading to pulmonary oedema

and, at higher doses, mortality. In order to understand the genetic basis of

this inflammatory cascade a custom micro array platform directed towards

immune and inflammatory markers was used in a Bal b/c mouse model of

inhalational ricin exposure. The gene which significantly differed from

the controls was identified .Key inflammatory markers associated with

ricin intoxication and several pathways that are altered in expression were

identified71

.

Dov Sitton et al studied the biosynthesis of Casbene, an anti-fungal

diterpene,in cell free extracts of Ricinus communis seedlings. They

compared the capacity of cell free extracts of 2.5-day-old castor bean

4CCl


28

seedlings for synthesis of casbene from mevalonic acid with the seedlings

which had been germinated under sterile conditions and seedlings which

were intentionally exposed to fungal cultures. Higher levels of casbene

were produced from the seedlings exposed to fungal cultures. Casbene

was found to inhibit the endogenous and gibberllic acid- simulated growth

of leaf sheaths of the dwarf -5 mutant of zea mays and the growth of

aspergillus niger and K-12 strain of Escherichia coli on nutrient medium.

Casbene may serve the castor bean plant as a phytoalexin72

.

Kumar et al studied oxidative stress associated hepatic and renal toxicity

induced by ricin in mice. Ricin, a glycoprotein from the Ricinus

communis seeds is known to have diverse toxic effects on cells of

different visceral organs. The hepatotoxicity, nephrotoxicity and oxidative

stress following i.p. administration of ricin (25µg/kg) in Swiss albino

male mice was studied. The results revealed that activities of various

enzymes were altered in various tissues. Blood urea level was also

increased. Blood creatinine and bilirubin were not altered. Lipid

peroxidation increased in hepatic and renal tissue. Total non-protein

sulfhydryl content decreased in plasma hepatic and renal tissues.

Superoxide dismutase activity decreased significantly in liver and kidney.

These results indicated that ricin produces hepatoxicity, nephrotoxicity

and oxidative damage at 24 h of post treatment. The hepatotoxicity was

more prominent than nephrotoxicity73

.

Anete et al studied the seizures elicited by ricinine. Ricinine, a neutral

alkaloid obtained form the plant Ricinus communis, induced seizures


29

when administered to mice at doses higher than 20mg/kg. Animals

presenting seizures showed a marked preconvulsive phase followed by

short duration hind limb myoclonus, respiratory spasms and death74

.

Francis Okwuasaba et al studied the anticonceptive and estrogenic effects

of Ricinus communis seeds. An ether-soluble fraction of a methanolic

extract of Ricinus communis seeds administered subcutaneously to adult

female rats and rabbits at doses up to 1.2g/kg and 6g/kg, respectively, in

divided doses showed anti- implantation and anticonceptive activities.

Laparotomy performed on day 10 and day 15 of pregnancy on mated

female rats and rabbits treated with the extract did not reveal any uterine

implantation sites. The animals were protected against pregnancy for over

three gestation periods and among those that later delivered, there was no

evidence of abnormality in the pups. In ovariectomized young female rats

as well as in immature mice, the amount of extract dose-dependently

increased uterine wet weight. Furthermore, the extract induced premature

opening of the vagina, increased the number of epithelial cells and

cornified cells and decreased the leucocyte number in the vaginal smear.

The estrogen-like activities exhibited by the extract were dose-dependent

and the anticonceptive effect may be due at least in part to such estrogenic

action75.

Rojas Hernandez et al evaluated the antimicrobial activity of indole

alkaloids in vitro. The alkaloids viz catharantine, vindoline, vindolinine,

perivine, reserpine, tabernaemontanine, tetrahydroalstonine, aparicine,

vindolinic acid, reserpic acid and vindolininol were faced to 40 bacterial


30

strains as well as to fungi and yeasts from different genera. The method

involving cylindric sections in a double agar layer was applied and

inhibition zones were measured76

.

Henriques et al studied the genotoxic effect of different groups of

alkaloids in prokaryotic and eukaryotic organisms. Voacristine isolated

from the leaves of Ervatamia coronaria showed invivo cytostatic and

mutagenic effects in Saccharomyces cerevisiae haploids cells77

.

Melo et al reported the cytostatic, cytotoxic and mutagenic effects of

voacristine in wild-type and repair-deficient yeasts. Voacristine, an indole

alkaloid isolated from the leaves of Ervatamia coronaria had dose-

dependent cytostatic and cytotoxic effects on cultures of Saccharomyces

cerevisiae. The lesions induced by voacristine in vivo were likely to be of

the adducts type and the damage was repairable in the wild-type of

yeasts78

.

31

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AIMS AND OBJECTIVES OF THE PRESENT WORK

In underdeveloped countries, traditional and herbal medicine including

folk medicinal practice scatters to most of the population because of accessibility,

affordability as well as the time tested dependability. They still depend on herbal

medicine because of the threat from side effects of the majority of the modern

drugs.

Liver disease is a leading cause of death in many countries and the

causative factors are alcohol consumption, malnutrition, anemia, hepatotoxic

drugs and infections etc. The liver, a vital organ instrumental in metabolism,

detoxification and elimination, is responsible for protection of human body

against adverse effects of drugs, chemicals, toxins, bacteria, viruses and parasites

etc., but in the process liver it self is under threat and obviously needs protection.

So far, no effective measures are available for the treatment of liver

diseases. The different medical, surgical and therapeutic methods used at present

are inadequate and are with generally poor terminal benefits. Also, some of the

modern drugs which are given to treat liver diseases may themselves cause liver

damage.

It is therefore, felt necessary to search alternative drugs for the treatment

of liver diseases to replace the existing drugs of uncertain efficacy and safety. In

this context the present study can be considered as an attempt to isolate

components of medicinal importance from the leaves of Ricinus communis and

scientific characterization of the phytochemical constituents besides

contemplating pharmacological studies form the leaves and seeds of Ricinus

communis in order to understand the hepatoprotective activity, anti-inflammatory

and analgesic properties.

review of litrature - shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/8127/10/10_chapter...

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