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Characterization of Psyllium (Plantago ovata) Polysaccharide and Its Uses

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The Plantago is one of the genera in family Plantaginaceae, a large genus of herbs or sub-herbs distributed mostly in the temperate region and a few in the tropics. Psyllium has been in use as a medicinal agent since ancient times throughout the world. It is used for treatment of constipation, diarrhea, hemorrhoids, and high blood pressure. In olden days it was also used topically to treat skin irritations, such as poison ivy reactions and insect bites and stings. The husk of the seeds of various species of psyllium is used for its medicinal properties. The primary ingredient of the seeds and husk is a mucilaginous polysaccharide. Psyllium has been reported for the treatment of constipation, diarrhea, and irritable bowel syndrome, inflammatory bowel disease (ulcerative colitis), colon cancer, diabetes, and hypercholesterolemia. When mixed with water, the therapeutic efficacy of the drug is due to the swelling of the mucilaginous seed coat which gives bulk and lubrication. Psyllium increases the volume of the feces by absorbing water in the gastrointestinal tract, which stimulates peristalsis. Modification of the polysaccharide by cross-linking or derivatization has been done to investigate its use as pharmaceutical excipient with multifarious roles. Various cross-linkers that have been studied include methacrylamide, N,N-methylenebisacrylamide, and polymethacrylamide.
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Characterization of Psyllium (Plantago ovata) Polysaccharide and
Its Uses
Ashwini R. Madgulkar, Monica R. P. Rao* and Deepa Warrier
Department of Pharmaceutics, AISSMS College of Pharmacy, Pune, India
Abstract
The Plantago is one of the genera in family Plantaginaceae, a large genus of herbs or sub-herbs
distributed mostly in the temperate region and a few in the tropics. Psyllium has been in use as a
medicinal agent since ancient times throughout the world. It is used for treatment of constipation,
diarrhea, hemorrhoids, and high blood pressure. In olden days it was also used topically to treat skin
irritations, such as poison ivy reactions and insect bites and stings. The husk of the seeds of various
species of psyllium is used for its medicinal properties. The primary ingredient of the seeds and husk
is a mucilaginous polysaccharide. Psyllium has been reported for the treatment of constipation,
diarrhea, and irritable bowel syndrome, inammatory bowel disease (ulcerative colitis), colon
cancer, diabetes, and hypercholesterolemia. When mixed with water, the therapeutic efcacy of
the drug is due to the swelling of the mucilaginous seed coat which gives bulk and lubrication.
Psyllium increases the volume of the feces by absorbing water in the gastrointestinal tract,
which stimulates peristalsis. Modication of the polysaccharide by cross-linking or derivatization
has been done to investigate its use as pharm aceutical excipient with multifarious roles. Various
cross-linkers that have been studied include methacrylamide, N,N-methylenebisacrylamide, and
polymethacrylamide.
Keywords
Psyllium; Ispaghula; Dietary bers; Constipation; Irritable bowel syndrome; Cancer; Hyperlipid-
emia; Acrylamides; Excipients
Abbreviations
AAm Acrylamide
APS Ammonium persulfate
DNA Deoxyribonucleic acid
GLUT-4 Glucose transporter protein
HEMA Hydroxylethylmethacrylate
HLA-B2712 Human leukocyte antigen
IBS Irritable bowel syndrome
IP Indian Pharmacopoeia
*Email: monicarp_6@hotmail.com
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LDL Low-density lipoprotein
MAAm Methacrylamide
N,NMBAAm N,N-methylenebisacrylamide
NVP N-vinylpyrrolidone
PAM Polyacrylamide
PMA Polymethacrylic acid
PVA Polyvinyl alcohol
RAPD Random amplied polymorphic DNA
SCFA Short-chain fatty acids
SHP Seed husk of psyllium
1 Introduction
Natural carbohydrates are the worlds most abundant, renewa ble, and biodegradable polymers. They
are the most basic source of fuel for all life forms on earth. The simplest carbohydrates are the
monosaccharides such as glucose, fructose, galactose, xylose, and mannose. Polysaccharides are
complex carbohydrate polymers consisting of two or more monosaccharides linked together
covalently by glycosidic linkages in a condensation reaction. They are usually insoluble in water
because of their large molecular size. Polysaccharides can be classied as homopolysaccharides and
heteropolysaccharides. A homopolysaccharide is one with repeat units of a single type of mono-
saccharide, whereas a heteropolysaccharide is composed of two or more types of monosaccharides.
In both types of polysaccharide, the monosaccharides are linked in a linear or branched fashion.
Polysaccharides are extremely important in organisms for the purposes of energy storage and
structural inte grity (Berg 2007).
Starch is used as a storage polysaccharide in plants in the form of both amylose and the branched
amylopectin. Cellulose and chitin are examples of structural polysaccharides. Cellulose is used in
the cell walls of plants and other organisms and is said to be the most abundant organic molecule on
earth. Chitin has a similar structure but has nitrogen-containing side branches, increasing its
strength. Polysaccharides also include callose or laminarin, chrysolaminarin, xylan, arabinoxylan,
mannan, fucoidan, and galactomannan (Campbell 1996).
Complex carbohydrates are important dietary elements for humans and are commonly called as
dietary bers. Dietary bers are classied as soluble and insoluble bers. Soluble bers cause an
increase in intestinal transit time of food and are readily fermented in the colon into gases. Insoluble
bers may be metabolically inert and provide bulk to intestinal contents or may undergo fermen-
tation in the large intestine. Insoluble bers tend to hasten movement of food through the intestine
(Dietary Reference Intakes for Energy et al. 2005; Eastwood and Kritchevsky 2005). Soluble bers
reportedly bind to bile acids in the small intestine, thereby reducing their absorption. This conse-
quently leads to lower cholesterol levels in the blood (Anderson et al. 2009). Soluble bers also
interfere with the absorption of sugar, regularize blood lipid levels, and produce short-chain fatty
acids as by-products of fermentation in the colon with wide-ranging physiological activities.
Although insoluble bers are associated with reduced diabetes risk, the mechanism by which this
occurs is unknown (Weickert and Pfeiffer 2008 ).
Modern lifestyle has given rise to a plethora of diseases including diabetes, cancer, and cardio-
vascular diseases. The short-term and long-term side effects associated with the therapeutic regimen
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used for control of these conditions have shifted the focus to alternative methods of prevention, cure,
and control which can work complementarily with the treatment. This in turn has spawned a
worldwide interest in the benets of dietary bers, the so-called wonder food of the new millennium.
Dietary ber is regarded as important for the diet, with regulatory authorities in many developed
countries recommending increase in ber intake (Dietary Reference Intakes for Energy et al. 2005;
Eastwood and Kritchevsky 2005; European Food Safety Authority 2014; Jones and Varady 2008).
1.1 Polysaccharides as Pharmaceutical Excipients
Excipients are an integral part of pharmaceutical dosage forms and comprise the greatest proportion
in dosage units. Knowledge of the composition, function, and behavior of excipients is a prerequisite
for the successful design, development, and manufacture of pharmaceutical dosage forms. Interest in
the physical effects and properties of the excipients used in pharmaceutical formulations has
increased in recent years due to the awareness of the fun damental effect that excipients can exert
on the bioavailability, bioequivalence, and stability of formulations.
Globally, there is a renewed interest in investigating drugs and excipients from natural sources,
especially from plant and marine sources that include starches obtained from corn, wheat, rice, and
tapioca (Andreev 2004) and different types of essential and aromatic oils. A number of poly-
saccharides like chitosan (Park et al. 2002; Sakkinen et al. 2003; Thanou et al. 2000), tamarind
seed polysaccharide (Gholardi et al. 2000; Kulkarni et al. 2005; Sumath and Ray 2002; Miyazaki
et al. 1998), psyllium husk (Fischer et al. 2004a), guar gum (George and Abraham 2007), xanthum
gum (Attama et al. 2006; Khoureeh et al. 2007), and rice bran wax (Dolz et al. 2007) are currently
being used or investigated for varied roles as pharmaceutical excipients which include
mucoadhesion, gel former, drug release retardant, plasticizer, thickener, and binder. The investiga-
tions to explore and investigate newer and newer plant sources continue unabated despite the
availability of a large number of synthetic excipients.
2 Psyllium
Psyllium has been in use since ancient times throughout the world. In India the use of P. ovata dates
back to 1500 BC in the Ayurvedic system of medicine, whereas the Chinese have used it in
traditional medicine for thousands of years. The European use of the herb dates back centuries,
and in North America, psyllium gained prominence in healing only near the end of the twentieth
century (http://savoursomepsyllium.blogs pot.in/2010/11/historytraditional-use.html 2014; Truestar
Health: http://www.truestarhealth.com/Notes/2150006.html#Traditional-Use 2014). The Indian and
the Chinese have used psyllium since 1500 BC for treatment of constipation, diarrhea, hemorrhoids,
bladder problems, and high blood pressure. It was also used topically to treat skin irritations, such as
poison ivy reactions and insect bites and stings. Europeans and North Americans began using
psyllium for cholesterol and blood glucose-lowering effects (http://www.psylliums.com/psyllium.
htm 2014). Typically, psyllium was administered in powder, akes, or granular form. These would
then be diluted in liquids and drank or sprinkled over meals. Only recently have they been made
available in tablets, capsules, and liquid forms (http://savoursomepsyllium.blogspot.in/2010/11/
historytraditional-use.html 2014; Bluementhal et al. 1998).
2.1 Biological Source
The dried, ripe seeds of Plantago afra (Plantago psyllium), Plantago indica (Plantago arenaria),
and Plantago ovata (Plantaginaceae) are used in medicine. The US National Formulary includes all
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three species under the name Plantago Seed (Trease and Evans 2008). Psyllium husk is the
cleaned, dried seed coat (epidermis) separated by winnowing and thrashing from the seeds of
Plantago ovata Forskal. It is commercially referred to as blond psyllium or Indian psyllium or
ispaghula. The husk may also be obtained from Plantago psyllium Linne or from Plantago indica
Linne (Plantago arenaria Waldstein et Kitaibel) commonly known as Spanish or French psyllium
(Plantaginaceae), in whole or in powdered form (United States Pharmacopoeia 2006). As per British
Pharmacopoeia, psyllium seed consists of the ripe, whole, dry seeds of Plantago afra L. (Plantago
psyllium L.) or Plantago indica L. (Plantago arenaria L. Waldstein and Kitaibel) (British pharma-
copoeia 1968). According to IP, ispaghula husk (isabgol husk, Plantago) consists of the epidermis
and collapsed adjacent layers removed from the dried ripe seeds of Plantago ovata Forsk (Indian
Pharmacopoeia 2010).
2.2 Geographical Source
Ispaghula is an annual herb cultivated in India in the states of Gujarat, Maharashtra, Punjab, and in
parts of Rajasthan and Sindh Province of Pakistan (Rangari 2008). Plantago psyllium is cultivated in
France and Spain for the European market. Plantago ovate seeds are cultivated in Southern Europe,
North Africa, and West Pakistan (Gupta 2005). India exports about 90 % of the gross production of
ispaghula and nearly 93 % of the export being husk. Psyllium husks and industrial powders are
exported in countries such as USA, UK, France, Germany, Japan, Indonesia, Canada, Mexico,
Sweden, Spain, Norway, Italy, Australia, Denmark, Korea, Pakistan, and some Gulf countries. The
USA is the largest buyer of ispaghula from India and accounts for about 75 % of the total husks
exports from India (http://www.psylliums.com/psyllium.htm 2014) (Table 1).
2.3 Cultivation, Collection, and Treatment
The crop requires marginal, light, well-drained sandy-loam to loamy soils having pH between 7 and
8. The plant does not have any specic nutrient requirement. It requires a cool climate and dry sunny
weather during harvesting. Mild dew, cloudy, or light showers cause seed shedding (Trivedi 2004).
Seeds are sown by broadcasting method in sandy, loamy soil. Addition of farmyard manure or
animal manure (prepared basically using cow dung, cow urine, waste straw, and other dairy wastes)
has favorable effect but generally ammonium sulfate is added as a fertilizer. Irrigation is done
regularly at an interval of 810 days. Ispaghula is not signicantly affected by pests or diseases, but
the annual harvest greatly suffers due to storm and rainfall. Plantago wilt Fusarium oxyspirum
and downy mildew are the major diseases of ispaghula. White grubs and aphids are the major insect
pests. The crop is harvested when the ower spikes turn reddish brown, lower leaves dry, and upper
leaves turn yellow. Harvested seeds are dried below 12 % moisture to enable cleaning, milling, and
storage (Rangari 2008). Ispaghula husk is separated from the seed by crushing in at stone grinding
mills by winnowing. It is marketed as a separate commodity. It is more in demand and fetches more
price than that of seeds. Raw psyllium seeds are fumigated in their storage area to avoid any
Table 1 Properties of psyll ium seeds
Characters Plantago ovata Plantago afra Plantago indica
Origin India, Pakistan Cuba, Spain, France Egypt, Medi terranean, Europe
Color Dull pinkish gray brown Glossy deep brown Dull blackish brown
Shape Boat shaped; outline ovate Boat shaped; outline elongated ovate Boat shaped; outline elliptical
Length 1.83.3 mm 2.03.0 mm 2.02.5 mm
Weight of 100 seeds 0.150.19 g 0.090.10 g 0.120.14 g
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contamination. Psyllium products like husk and powder are treated in the fumigation chamber with
approved chemical reagents like methyl bromide as per latest international guidelines. Psyllium
products can also be sterilized by ethylene oxide or gamma radiation, if required (http://phytosani-
torysolution.com/ 2014). Seeds and husks of Plantago major Linn, Plantago lanceolata Linn,
Plantago psyllium Linn, as well as seeds of Lepidium sativum are used as adulterants in ispaghula
(http://www.psylliums.com/psyllium.htm 2014).
2.4 Morphology
Psyllium seeds are ovoid-oblong in shape, about 23 mm long and 0.81.5 mm wide (Fig. 1). They
are pinkish gray to brown in color with a convex dorsal surface and concave ventral surface with a
deep groove running lengthwise along the center (http://www.psylliums.com/psyllium.htm 2014)
(Figs. 2 and 3a, b).
Fig. 1 Morphology of psyllium seeds [Plantago ovata]
Fig. 2 Transverse section of seeds of Psyllium ovate
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2.5 Microscopy
The transverse sections of the seed that cut through the central region possess a reniform outline and
exhibit a spermoderm, endosperm, and embryo. The spermoder m shows an outer epidermis of
mucilaginous epidermal cells with obliterated walls in glycerine mounts; the radial and inner walls
swell and disintegrate to form a clear mucilage upon irrigation of the mount with water, and a
pigment layer with brown amorphous content. The endosperm is composed of irregular-shaped,
thick-walled cells with walls of reserve cellulose. The outer layer of this region consists of palisade
cells 1540 mm in height. Aleurone grains and xed oils are found in the endosperm cells (Bruneton
1995).
2.6 Chemical Constituents
Many elements have been identied in the seed which include proteins, lipids, sterols, triterpenes,
and aucubin glycoside. The mucilage level is about 30 %. The principal constituent of the mucilage
is 85 % of a soluble polysaccharide fraction dominated by
D-xylose. The polymer backbone is a
xylan with 1!3 and 1! 4 linkages with no apparent regularity in their distribution. The mono-
saccharides in this primary chain are substituted on C-2 or C-3 by
L-arabinose, D-xylose, and
a-
D-galactouronyl-(1!2)-L-rhamnose (Bruneton 1999). Psyllium seed mucilage contains 22.6 %
arabinose, 74.65 % xylose and traces of other sugars, and 35 % nonreducing terminal residues
(Fischer et al. 2004b).
2.7 Structure
The polysaccharide structure constitutes a densely substituted main chain of (1!4)-linked
D-xylopyranosyl residues, some carrying single xylopyranosyl side chains at position 2, others
Fig. 3 (a) Chemical structure of arabinosyl (galactouronic acid) rhamnosylxylan. (b) Ball-and-stick model of
arabinosyl (galactouronic acid) rhamnosylxylan
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bearing, at position 3, trisaccharide branches having the sequence 1-Araf- (1! 3)-1-Araf. Chemi-
cally the polysaccharide is arabinosyl (galacturonic acid) rhamnosylxylan.
3 Clinical Indications
Psyllium has been reported for the treatment of constipation, diarrhea, and irritable bowel syndrome,
inammatory bowel disease (ulcerative colitis), colon cancer, diabetes, and hypercholesterolemia
(Majmudar et al. 2008; Reynolds 1993).
3.1 Constipation
Psyllium husk is widely used for treatment of constipation due to its mucilaginous components.
When mixed with water, the therapeutic efcacy of the drug is due to the swelling of the
mucilaginous seed coat which gives bulk and lubrication (Tyler et al. 1988 ). Psyllium increases
the volume of the feces by absorbing water in the gastrointestinal tract, which stimulates peristalsis
(Read 1986). The intraluminal pressure is decreased, colon transit is increased, and the frequency of
defecation is increased (Martea u et al. 1994 ; Sölter and Lorenz 1983). The effectiveness of ber, and
psyllium in particular, on constipation depends on the main cause of the constipation. In a study of
149 patients with chronic constipation, the consumption of 1530 g daily of a psyllium seed
preparation provided bowel relief in 85 % of participants who had no known pathological cause
for their constipation. Only 20 % of individuals with slow transit responded to psyllium. A slightly
greater percentage (37 %) of those with disorders of defecation including rectocele, internal
prolapse, anismus, and rectal hyposensitivity found improvement (Alternative Medicine Review
2002; Voderholzer et al. 1997; Kumar et al. 1987; Qvitzau et al. 1988).
3.2 Fecal Incontinence
Psyllium has been shown to have the paradoxical property of both improving constipation by
increasing stool weight and ameliorating chronic diarrhea. Because of its ability to retain water,
psyllium has also been shown to benet ind ividuals with fecal incontinence from liquid stools or
diarrhea. A placebo-controlled trial of person s with liquid stool fecal incontinence was performed in
which supplementation with both gum arabic and psyllium showed approximately a 50 % decrease
in the occurrence of incontinent stools. The psylliu m group had the highest water-holding capacity
of water-insoluble solids and total water-holding capacity of the stool (Alternative Medicine Review
2002; Bliss et al. 2001).
3.3 Hemorrhoids
With the known benet of psyllium for both constipation and loose stools, psyllium was also
reported to be benecial for the treatment of hemorrhoids. It was found to have a signicant
improvement in reduction of bleeding and a dramatic reduction of congested hemorrhoidal cushions
(Perez et al. 1996; Broader et al. 1974; Webster et al. 1978).
3.4 Irritable Bowel Syndrome (IBS)
Constipation is characterized by unsatisfactory defecation and infrequent stools, difcult stool
passage, or both. On the other hand, the presence of clinically important abdominal discomfort or
pain associated with constipation denes IBS with constipation. Intake of psyllium may be effective
in alleviating chronic constipation in patients without slow colonic transit or disordered constipa-
tion. On the other hand, ber with lactulose may improve stool consistency in patients with IBS with
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constipation. The easing of bowel dissatisfaction appears to be a major reason for the therapeutic
success of psyllium in IBS (Degan and Phillips 1996; Bouchoucha et al. 2004; Koch et al. 1997).
3.5 Ulcerative Colitis (Crohns Disease)
The two primary sites for Crohns disease are the ileum, which is the last portion of the small bowel
(ileitis, regional enteritis), and the colon (Crohns colitis). A small number of studies have examined
the ability of psyllium to maintain remission in ulcerative colitis. Dietary ber has been proven to be
benecial in maintaining remission in human ulcerative colitis, an effect related with an increased
luminal production of short-chain fatty acids (SCFA), i.e., acetate, propionate, and butyrate in the
intestines. Dietary ber supplementation ameliorated colonic damage in HLA-B2712. In an open
label, randomized, multicenter trial of persons with ulcerative colitis, psyllium seed supplementation
(10 g twice daily) was as effective as mesalamine in maintaining emission. It was inferred that this
effect may possibly be due to increased levels of butyric acid with psyllium supplementation
(Alternative Medicine Review 2002; Fernandez et al. 1999 ).
3.6 Appetite
Psyllium may also have an effect on appetite. A triple-blind study on 17 women looked at the effect
of 20 g of psyllium seed 3 h pre-meal and again immediately post-meal during three 3-day study
periods. The subjects reported signicantly increased feelings of fullness 1 h after meals with the
psyllium and exhibited a signicantly lower fat intake with those meals (Turnbull and Thomas
1995).
3.7 Hyperlipidemia
Psyllium has been shown to reduce total cholesterol and low-density lipoprotein (LDL) cholesterol
in animals and in humans (Fernandez 1995; Fernandez et al. 1995; Terpstra et al. 2000). Sprecher
et al. demonstrated a 3.5 % reduction in total cholesterol and a 5.1 % reduction in LDL levels after
consuming 5 g of psyllium husk twice daily for 8 weeks (Sprecher et al. 1993). Another study began
with individuals on the American Heart Association Step 1 diet, followed by 8 weeks of psyllium,
resulting in decreased total cholesterol (4.8 %) and LDL (8.8 %) (Bell et al. 1989). A meta-analysis
was performed on eight trials of psyllium husk in conjunction with a low-fat diet in the treatment of
hypercholesterolemia. After an initial 8-week, low-fat diet run-in, 10.2 g psyllium was given per day,
resulting in a 4-percent reduction in serum total cholesterol and a 7-percent reduction in LDL
cholesterol, compared to diet and placebo. A 6 % reduction in the ratio of apolipoprotein (apo) B to
apo A-I was also noted (Anderson et al. 2000a; Levin et al. 1990; Anderson et al. 2000b; Olson
et al. 1997). A meta-analysis of 12 studies of psyllium-enhanced cereal product consumption on
total and LDL cholesterol in 404 adults with mild to moderate hypercholesterolemia demonstrated a
reduction of 5 % of total cholesterol and 9 % of LDL cholesterol (Romero et al. 1998). Researchers
studied the effect of ber-enhanced cookies on blood lipids in hypercholesterolemic men, using
wheat bran-, psyllium-, or oat bran- containing cookies (wheat bran was used as the placebo since it
has no demonstrated cholesterol-lowering effect). At the end of the 8-week study, plasma LDL
cholesterol had decreased to 22.6 % in the psyllium group and 26 % in the oat bran group (Burton
and Manninen 1982). A 4-month study of 12 elderly patients showe d psyllium husk reduced total
serum cholesterol by 20 %, a gure much higher than the abovementioned studies [(Ste wart
et al. 1991)]. In another study, a signicant reduction in total serum cholesterol was noted in
176 elderly persons who used psyllium for 1 year (Vega-Lopez et al. 2001). The authors found
that for every 1 g increase in daily psyllium dose, there was a 0.022-mmol/l (0.84 mg/dl) decrease in
serum total cholesterol concentration. In a study to examine age and gender differences in the effect
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of psyllium on blood lipids, men and pre- and postmenopausal women were given psyllium (15 g
daily) or placebo. Psyllium lowered plasma LDL cholesterol by 79 % in all groups. Triglyceride
levels were lowered by 17 % in men, but were increased by 16 % in postmenopausal women.
Premenopausal women displayed no signicant shift in triglycerides (Agrawal and Pariddhavi
2012).
The mechanism of action of psylliums hypocholesterolemic effects has not been fully
expounded. Psyllium was shown to stimulate bile acid synthesis (7 a-hydroxylase activity) in
animal models (Horton et al. 1994; Matheson et al. 1995) and in humans (Everson et al. 1992).
The diversion of hepatic cholesterol for bile acid production is an established mechanism for
reducing serum cholesterol. Psyllium s effect on the absorption of cholesterol (Everson
et al. 1992; Turley et al. 1994) and fat (Ganji and Kies 1994) is negligible but may appear to
contribute to cholesterol lowering. Additional mechanisms, such as inhibition of hepatic cholesterol
synthesis by propionate (Anderson 1995) and secondary effects of slowing glucose absorption
(Jenkins et al. 1990), may also play a role.
3.8 Diabetes Mellitus
Dietary bers from psyllium have been used extensively in processed food to aid weight reduction,
for glucose control in diabetic patients (Anderson et al. 1999). It has been shown to improve
postprandial glycemic index and insulin sensitivity. In rats it was found to suppress sucrose and
glucose absorption in the gastrointestinal tract. Studies also showed enhanced blood glucose
disposal by regulating skeletal muscle plasma membrane GLUT-4 protein (glucose transporter)
expression without phosphatidylinositol 3-kinase activation (Yu et al. 2009). The effect of psyllium
husk was studied in 34 men with type 2 diabetes and hypercholesterolemia, given either placebo or
5 g psyllium twice daily for 8 weeks. Total cholesterol was lower by 8.9 % and LDL by 1 %. In
addition, the postprandial rise of glucose was signicantly reduced (Duke 1985). The mechanism for
hypoglycemic effect in humans may be due to suppression of diffusion of glucose to small intestinal
epithelium for absorption, delayed gastric emptying time, and reduced carbohydrate digestibility by
retarding their access to digestive enzymes (Liangli and Wei Liu 2012).
3.9 Cancer
Seeds of Plantago coronopus, P. lanceolata, P. ovata , and P. psyllium were used by humans against
cancer (Liangli and Wei Liu 2012; Hartwell 1982). Besides, the presence of luteolin-7-O-
b-glucoside, a major avonoid present in the leaves of P. serraria, P. psyllium, P. coronopus, and
P. lanceolata , was able to strongly inhibit the proliferation of human cancer cell lines (Galvez
et al. 2003). Butyric acid which is reported to exhibit antineoplastic activity against colorectal cancer
is the preferred oxidative substrate for colonocytes and may be helpful in the treatment of ulcerative
colitis (Whitkus et al. 1994). Butyrate may also dose-dependently suppress cancer cell proliferation,
promote differentiation marker expression, and lead to reversion of cells from a neoplastic to
nonneoplastic phenotype (Yu et al. 2009). In a study of patients with resected colorectal cancer,
those given 20 g of psyllium seeds daily for 3 months exhibited an average increase of butyric acid
production of 42 %, which decreased to pretreatment levels within 2 months of cessation of
supplementation (Nordgaard et al. 1996).
Psyllium might also alter colonic sphingomyelin metabolism and apoptosis which may have an
impact on colon tumorigenesis and inammation in mice (Cheng et al. 2004).
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4 Safety Data
4.1 Precautions
The recommended dose for psyllium varies as per the age and clinical indication. Nonetheless the
precautions are common regarding safe use of psyllium. Psyllium should not be taken in case of
suspected intestinal obstruction (ileus), diseases of the esophagus, and patients with difculty in
swallowing. It is also not recommended for patients with intestinal atresia and stenosis and for
children below 6 years. It should be consumed with sufcient quantity of water, failing which may
cause choking due to blockage of the throat or esophagus (New HMPC Commission 2014).
4.2 Drug Interactions
Bulking agents have been reported to reduce the absorption of some minerals (calcium, magnesium,
copper, and zinc), vitamin B
12
, cardiac glycosides, and coumarin derivatives (Gattus o and Kamm
1994;H
ansel et al. 1994a; Drews et al. 1981). The co-administration of psylliu m with lithium salts
has been reported to reduce the plasma concentrations of the lithium salts due to inhibition of their
absorption from the gastrointestinal tract (Pearlman 1990). It has also been reported to decrease both
the rate and extent of carbamazepine absorption, inducing subclinical levels of the drug. Therefore,
ingestion of lithium salts or carbamazepine and psyllium should not be concomitant (Etman 1995).
Insulin-dependent diabetic people may require less insulin if they are concurrently taking psyllium
(Bradley 1983).
4.3 Preclinical Safety Data
The material hydrates and swells to form mucilage in vivo as it is only partially solubilized. Less
than 10 % of the mucilage gets hydrolyzed in the stomach. Preclinical studies in various animal
species revealed pigmentation of various organs. Albino rats showed a dark pigmentation of the
suprarenal gland, kidney, marrow, and liver after 125 days on a diet of 25 % of psyllium seeds. Dogs
showed gray color of kidneys after a diet containing 25 % psyllium seeds for 30 days. Similar effects
were not observed in humans. The pigmentation could be attributed to the dark pigment in the
pericarp of the seeds (H
ansel et al. 1994b).
5 Preserving Genetic Integrity
Proper conservation and successful breeding of commercially viable crops is facilitated by appro-
priate identication of the plant. Conventionally, identication and classication of plant groups are
solely based on differences in morphological features, especially the oral character which was
considered to be consistent. It is well established that morphological characteristics are a result of the
interaction between the environment and the genotype and can also be inuenced by climatic and
edaphic factors. Molecular techniques using DNA markers are ther efore useful not only to identify
the genotypes for authentication, but also in assessing and exploiting the genetic variability
(Whitkus et al. 1994b). These techniques are suitable means for estimating genetic diversity because
of their abundant polymorphism and the fact that they are independent of environment (Gepts 1993).
DNA ngerprintin g is a remarkable tool to create the genetic blueprint of all medicinal plants.
Genetic diversity in ve cultivars of P. ovate was estimated using molecular markers by Pal (Pal and
Raychoudhuri 2004) and Raychoudhuri (Raychoudhuri and Pramanik 1997). Similarly, Vahabi
et al. used molecular and morphological markers for the evaluation of genetic diversity between
P. ovate (Vahabi et al. 2008). Wolff and Morgan-Richards used random amplied polymorphic DNA
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(RAPD) markers for differentiating subspecies of Plantago major (Wolff et al. 2000). Samantaray
et al. use d RAPD markers to assess genetic relationships and variance in seven species of Plantago,
i.e., P. ovata (Forsk.), P. indica (L.), P. arenaria (Waldst.), P. psyllium (Linn.), P. lanceolata (Linn.),
P. serraria (Linn.), and P. coronopus (Linn.) (Samantaray et al. 2010 ). In India, facilities have been
developed for long-term storage of germplasm in the National Gene Bank in New Delhi, India, to
avoid frequent regeneration and to check genetic drift (Trivedi 2004).
6 Chemical Modifications
A lot of work involving derivatization/cross-linking of polysaccharide obtained from psyllium seeds
and husk is underway. The objective of these studies is to modify the properties of the polysaccha-
ride in order to exploit it as a pharmaceutical excipient. Some of the pioneering works done in this
eld are enlisted below:
1. Singh and Sharma have developed psylliumPVAacrylic acid-based novel hydrogels for use in
antibiotic drug delivery through graft copolymerization. The use of a very small amount of these
petroleum products has developed low energy, cost-effective, biodegradable, and biocompatible
material for potential biomedical applications. In this experiment, polyvinyl alcohol and acrylic
acid were used as monomers; N,N-methylenebisacrylamide was used as the cross-linking agent,
and ammonium persulfate was used as the thermal initiator (Singh and Sharma 2010).
2. Patil et al. have developed and evaluated psyllium seed husk polysaccharide-based wound-
dressing lms. In this study, wound-dressing lms were fabricated using seed husk of psyllium
(SHP) complexed with povidone iodine and were evaluated for various physicochemical prop-
erties as well as wound healing activity in albino rats (Basavaraj et al. 2011).
3. Singh and Chauhan have prepare d psyllium- and acrylamide-/methacrylamide-based hydrogels,
and the effects of pH on the release dynamics of insulin from drug-loaded hydrogels were studied
to evaluate the drug release mechanism. Two types of hydrogels were prepared by using
acrylamide and a mixture of acrylamide/methacrylamide. The hydrogels were named as psy-cl-
poly (AAm) and psy-cl-poly (AAm-co-MAAm) hydrogels, respectively. N,
N-methylenebisacrylamide was used as the cross-linking agent and ammonium persulfate was
used as the thermal initiator (Singh and Chauhan 2010).
4. Sen et al. conducted research on a novel microwave-initiated method for synthesis of
polyacrylamide-grafted psyllium (Psy-g-PAM). Psyllium was modied through grafting of
polyacrylamide (PAM) chains on it using microwave radiations only, in the absence of any
other free radical initiator. The synthesized grades of the graft copolymer were characterized
through various physicochemical techniques. The occulation efcacy of the synthesized graft
copolymers was studied in kaolin and coal ne suspension through standard Jar test procedure.
It was found that the high occulation efcacy of Psy-g-PAM makes it a good candidate to be
used as a occulant for waste water treatment and treatment of efuents discharged from coal
washeries (Sen et al. 2010).
5. Singh and Kumar prepared psyllium-N-vinylpyrrolidone (NVP)-based hydrogels by radiation-
induced cross-linking. The reaction mixture was irradiated with gamma rays of a dose rate of
2.43 kGy/h, in 60 Co gamma chamber for a specic time. The cross-linking polymers thus formed
were named as psy-cl-poly (NVP) hydrogels. These hydrogels were then studied for their release
dynamics of anticancer model drug (5-uorouracil). It was found that the release of the drug from
the hydrogels occurred through non-Fickian diffusion mechanism (Singh and Kumar 2008).
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6. Kumar and Sharma synthesized a new material (Psy-g-PMA) by grafting polymethacrylic acid
onto the backbone of psyllium using a microwave-assisted method. Acetylsalicylic acid was
incorporated in the various Psy-g-PMA samples and tablets were prepared to study the in vitro
drug release. This biodegradable material is good for the fast release of medicine in acidic
environments such as the human stomach. The material also demonstrated superabsorbent
capacity for water and may be useful in diapers and feminine sanitary pads (Kumar and
Sharma 2013).
7. Singh and Chauhan prepared psyllium 2-hydroxylethylmethacrylate (HEMA) and acrylamide
(AAm)-based polymeric networks by using N,N-methylenebisacrylamide (N,N-MBAAm) as
cross-linker and ammonium persulfate (APS) as initiator. It was concluded that the swelling of
the modied psyllium-based hydrogels is affected by the composition of the hydrogels and pH of
the swelling medium (Singh et al. 2008).
7 Conclusion
The surge in the development of newer drug molecules for the treatment of a plethora of diseases has
denitely led to improved therapy, but it has also resulted in a concomitant rise in side effects and
adverse reactions. This has led to a resurgence of plant-based traditional systems of medicine and
nutraceuticals which either supplement or complement these therapeutic regimens. The impact of
the role of dietary bers, the wonder food of the new millennium, in the control and cure of many
lifestyle diseases cannot be underestimated. Psyllium has been in use since ages for its various
medicinal effects and continues to rule the roost for the treatment of constipation, diarrhea, irritable
bowel syndrome, inammatory bowel diseases, ulcerative colitis, colon cancer, diabetes, and
hypercholesterolemia. The high mucilaginous content of psyllium seeds and husk has also spawned
an interest in its use as pharmaceutical excipient. Chemical modications have been done to improve
its prole as multifunctional pharmaceutical excipient. Future studies could be aimed at exploring
and discovering more uses of this remarkable but unassuming plant.
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... Tüketim şekline göre de etkileri değişmektedir. Psyllium tohumunun genel yapısı Şekil 2'de gösterilmektedir (Madgulkar et al., 2014). Psyllium, tohumu ve kabuğunun besin içeriği farklılık gösterebilmektedir. ...
... Şekil 2. Psyllium (Plantago ovata) tohum yapısı (Madgulkar et al., 2014) Şekil 3. Pysllium tohumu ve kabuğunun besin içeriği (Shah et al., 2020). Şekil 3' de görüldüğü üzere Pysllium tohumu toplam besin içeriğine bakıldığında oldukça yüksek düzeyde diyet lifi içermekle birlikte bu lifin büyük çoğunluğu da çözünür lif özelliği göstermektedir. ...
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... The gel fraction isolated from the seeds showed significant cytoprotective effect due to the antisecretory action and by the effects on mucosal glycoproteins [15]. On the other hand, Psyllium has been reported in humans for the treatment of different gastrointestinal disorders such as constipation, diarrhea, irritable bowel syndrome, inflammatory bowel diasease and ulcerative colits [16]. ...
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