Pharmacology and Phytochemistry of Pakistani Herbs and Herbal Drugs Used for Treatment of Diabetes
Muhammad Nouman Sohail,
After twenty years Pakistan will be the fourth largest country with respect to the diabetic individuals. For a developing country like Pakistan availability of modren medical facilities to every person is not possible. In addition to economic constrains, reported side effects of these modern drugs encouroged us to search for an economical and safe alternative that can cure this disease. Herbal plants (cheaper availability and with less or no side effects) have emerged as a potential candidate. This review focuses the effectiveness of herbs and herbal drugs which are commonly used in Pakistan against diabetes. Different search engines were explored including Pubmed, Google and Asci database (up to 2nd June 2011) by using different keywords. Priority was given to research article and information given by authentic organizations and federations. Ninteen plants, which were used by local people as vegetable or herbal remedy, were analyzed for their antidiabetic potentials on the basis of previously published literature. Varying levels of antioxidant, antihyperlipidemic, Insulin stimulating, nephroprotective and hepatoprotective activities of these plants have been reported in various studies. Out of the ninteen herbs O. sanctum, Z. officinale, T. foenum-graecum and P. amarus were found to be the most effective against diabetes. In future adaptive use of these herbs in daily life as food may help to slow down the pace of disease development in Pakistan. There are plenty of herbs for which the medicinal value is still to be inquired so that they can replace and used as an alternate of synthetic drugs.
Received: February 06, 2011;
Accepted: May 09, 2011;
Published: June 14, 2011
Diabetes is a chronic disease that occurs either when the pancreas does not
produce enough insulin (a drug used for the treatment of diabetes) or when the
body cannot effectively use the insulin it produces (http://www.who.int/diabetes/en/)
(last time accessed on 27 April 2011), If untreated, it could result in kidney
and heart disease, stroke, blindness, loss of limbs and reduced life expectancy
(Expert Committee on the Diagnosis and Classification of
Diabetes Mellitus, 1997). There are mainly three types of diabetes type
1, type 2 and gestational diabetes mellitus (Alberti and Zimmet,
1998). Genetics plays an important role in the development of both type
1 and type 2 diabetes (Cooke and Plotnick, 2008). Destruction
of insulin producing beta cells of pancreas either by patients own immune
system or due to other factors ultimately results in the occurrence of type
1 diabetes (Cooke and Plotnick, 2008; Ylipaasto
et al., 2004). Destruction of beta cells is thought to be triggered
by a combination of different environmental factors in genetically susceptible
organisms. Type 2 diabetes is most prevalent among diabetic patents and is directly
linked with individuals suffering with a physiological disorder of insulin resistance
(Kahn et al., 2006). Factors like genetic susceptibility
of patient, diet and other environmental condition eventually leads towards
the development of type 2 diabetes (Riserus et al.,
2009; Ripsin et al., 2009). Another form of
diabetes, which only linked to females, is Gestational Diabetes Mellitus (GDM).
This form of diabetes is characterized as detection of increased blood glucose
levels during pregnancy (American Diabetes Association, 2010).
In a study of Australian population it was found that age of women positively
correlates with the occurrence of this disease (Templeton and
Pieris-Caldwell, 2008). Individuals suffering with this form of diabetes
are more prone to type 2 diabetes (Hoffman et al.,
STATUS OF DIABETES IN PAKISTAN
Around 180 million people worldwide suffer from diabetes, and the number is
predicted to reach 325 million by the year 2025 (Lefebvre,
2005). In 2007, 246 million people world-wide suffered from diabetes and
this number makes the disease as one of the most widespread global disease and
4th leading cause of death in the world. Report of IDF published in The Nation,
November 15, 2008. Almost 438 million people will suffer from diabetes in 2030
compare to 177 million in 2010 (Report by WHO published in News of future at
future_health.html). Among the 246 million diabetic people worldwide approximately
half are from Asian countries (http://www.asiandiabetes.org/).
In the list of ten most vulnerable countries (in term of number of people with
diabetes) of 2030 seven are from Asia (Wild et al.,
2004). It is also very alarming that diabetes develop in younger age in
Asian population than the white peoples (Ramachandran et
Pakistan is the 7th leading diabetic nation in the world and if this trend
keeps on increasing at same pace then after 20 years it will be ranked as 4th
largest country with respect to diabetes (http://ndpppk.com/dip.html).
In Pakistan 6.9 million people are affected by diabetes and this number will
rise up to 11.5 million by 2025 (Hayat and Shaikh, 2010).
According to International Diabetic Federation, prevalence of diabetes is more
in urban areas than rural, males are more prone to this disease than females,
and among the age groups 40-59 was having maximum percentage of
diabetic individual in Pakistan. Among four provinces of Pakistan, pervasiveness
of diabetes in adults was found to be highest in Sindh followed by Punjab, Balochistan
and Khyber Pakhton Khwa (http://ndpppk.com/dip.html)
(last accessed on 28-4-2011). Coordinated efforts from public and private sectors
are required to fight against this chronic disease.
Every plant could be a medicinal plant? No, according to WHO
(1977) a medicinal plant is any plant that can be used to synthesize valuable
drugs as one or more of its organs contain substances that can be useful for
medicinal purpose. According to World Health Organization more than 21,000 plants
are being in use as medicinal purpose around the world. A huge part of worlds
population (80%) employs herbal medicines to deals with their daily medical
issues (DaSilva et al., 2002). Twenty five percent
of drugs prescribed by Western pharmacists comprise of elements that are of
plant origin. Studies aiming at the development of rapidly propagating methods
for medicinal plants is an indication that demand for these plant is increasing
(Nalawade and Tsay, 2004; Huang et
al., 2000; Khan et al., 2004; Malik
et al., 2007; Banu and Bari, 2007; Jamil
et al., 2007; Gantait et al., 2010;
Satyavani et al., 2011a). Use of herbal medicines
is also very common among population of Pakistan (Hoareau
and DaSilva, 1999). Medicines based on herbal formulations usually have
lesser side effects and better compatibility with human body than modern medicines
(Kamboj, 2000). All those diseases like memory loss,
osteoporosis, diabetic wounds, alzheimer, immune and liver disorders etc. which
are not completely or partially curable with modern medicines are being treated
with herbal medicines (Gessner et al., 1985; Watanabe
et al., 2001; Kamboj, 2000). Less side effects,
better compatibility and only available treatment for some diseases makes the
herbal medicines an ideal remedy for treatment of the diseases.
NEED AND SCOPE OF HERBAL REMEDIES FOR DIABETES TREATMENT
There are different methods to treat diabetes with varying degree of success
like use of different drugs (intensive insulin therapy (IIT) (Qaseem
et al., 2011; Clement et al., 2004),
antibodies (monoclonal antibody (Herold et al., 2002))
and organ transplantation (Ryan et al., 2001).
Islet transplantation is one of the surgical methods used to treat type 1 diabetes.
In a study by Guignard et al. (2007) a total of
_ 7, 620 were calculated for one islet transplantation. Type 2 diabetes is not
insulin dependent and many different drugs have been employed to treat this
disease. Metaformin is a drug used to treat type 2 diabetes. Long term use and
high doses of this drug are associated with malabsorption of vitamin B12 and
lactic acidosis development, respectively (Bailey and Turner,
1996; Salpeter et al., 2006). Some drugs like
sulfonylureas and thiazolidinediones were used to treat type 2 diabetes and
found to be linked with hypoglycemia and increase in both body weight along
with increased risk to develop cardiovascular disease (Groop,
1992; Meinert et al., 1970; Kahn
et al., 2006; Singh et al., 2007).
Glinides and α-Glucosidase inhibitors are also used to treat non-insulin
dependent diabetes; frequent administration of these drugs is required to reduce
the glucose levels in blood (Malaisse, 2003; Van
de Laar et al., 2005). Each drug have some disadvantages like chances
of developing other diseases, so frequent and careful administration of these
drugs should be considered as all of above drugs are very expensive (Nathan
et al., 2009). In a country like Pakistan where low value healthcare
practices has been performed and 24% of its population lives below the line
of poverty, treatment of diabetes with expensive drugs and surgical methods
is not feasible (https://www.cia.gov
last time access on 20-03-2011). So in Pakistan being a developing country use
of herbs is inevitable as a cheaper source of medication to treat highly prevalent
disease such as diabetes.
Pharmacological characterisitics and phytochemistry of Herbs and Herbal Drugs used for treatement of Diabetes is given below:
Allium cepa: Allium cepa L. is the common onion that belongs
to family Alliaceae (Rose et al., 2005; Nithya
and Ramachandramurty, 2007). Mainly onion bulbs are white, yellow or red,
stems are green and leaves are hollow (Farooqi and Kumar, 2003).
It is a cultivated crop in various areas of Pakistan (Malik
et al., 2003) and its juice is used as a remedy to treat diabetes
and high blood pressure (Ahmad et al., 2009).
Antifungal and antioxidant properties of its extract are also well proven (Tagoe
et al., 2011; Ige et al., 2011). Onion
is a rich source of dietary flavonoids (Slimestad et al.,
2007; Sharif et al., 2010). Some flavonol
glucosides of onion were found to be very stable under commercial storage conditions
(Price et al., 1997). Flavonol glycosides are
thought to have antidiabetic activity due to their inhibitory effect on glycation
(Kim et al., 2004). Maillard reaction is a part
of human glycation process (Horiuchi et al., 1991).
Kousar et al. (2008) found negative effect of
onion extract on maillard reaction. So this inhibitory effect on maillard reaction
could be one of the factors contributing for its antidiabetic effect. Different
sulfur containing compounds also contribute for antidiabetic activity of onion.
This was confirmed by Kumari et al. (1995) who
studied the antidiabetic effect of an amino acid (S-methyl cysteine sulphoxide)
isolated from onion. They found that the results were significant in lowering
the blood glucose levels of rats. This compound was also found to have anti-hyperlipidemic
activity (Kumari and Augusti, 2007). Consumption of onion
in large quantity could have serious health hazards as some compounds possess
inhibiting effects on thiol group enzymes (Augusti, 1996).
Diet consisting of 6% Allium cepa resulted in impaired growth of male
Wistar rats (Abdel Gadir et al., 2006), no harmful
effect was observed on 2% diet (Abdel-Gadir et al.,
Allium sativum: Allium sativum (garlic) is a herb bearing
an underground bulb made up of flashy cloves that are used all over the world
to reduce the vulnerable effects of most of the diseases. Garlic is also used
in food as flavoring agent and spice, its strong order and flavor is due to
the presence of sulphur compounds (Thomson et al.,
2007). Antioxidant, antifungal, antimicrobial and antidiabetic, properties
of its extract has been reported in many studies (Avci et
al., 2005; Ogungbe and Lawal, 2008; Abera
et al., 2011; Butkhup and Samappito, 2011;
Masaadeh et al., 2006; Philip
et al., 2009; Shokrzadeh and Ebadi, 2006; Hasan
et al., 2005; Sukandar et al., 2010).
It is locally know as Thoom and its underground part is used for
diabetes and hypertension (Ahmad et al., 2009;
Ishtiaq et al., 2007). A range of compounds (alkaloids,
amino acids, carbohydrates, cardiac glycoside, flavonoids, ketones, lipids,
phenol, reducing sugars, saponins, steroids, terpene) are present in it (Olusanmi
and Amadi, 2009; Pathmanathan et al., 2010;
Mikail, 2010). Kumar and Reddy (1999)
studied the effect of ethanol extract of garlic on alloxan induced diabetic
mice. They found significant decrease in blood glucose levels. Garlic contains
a variety of sulfur based compounds, which are mainly in the form of cysteine
derivatives (Augusti, 1996). A sulfur containing amino
acid (S-allyl cysteine sulphoxide) isolated form Allium sativum showed
significant antidiabetic activity in alloxan diabetic rats (Sheela
and Augusti, 1992; Augusti and Sheela, 1996). Its
antidiabetic activity was almost same as those of glibenclamide and insulin.
In addition better performance of this compound as hypolipidemic agent makes
it more appropriate to deal with both diabetes and hyperlipidemia. Diet consisting
of 6% Allium sativum produced impaired growth in male Wistar rats (Abdel
Gadir et al., 2006).
Aloe vera: Aloe vera is being used as medicinal plant
since many years (Subramanian et al., 2006a,b,
2007). Leaves of this plant are green resembles with
cactus leaves and filled with a clear gel like fluid, which is viscous in nature
(Singh et al., 2010). In addition to its medicinal
values it is also employed in poultry, dairy and as insecticide (Moorthy
et al., 2009; Mmereole, 2011; Odo
et al., 2010; Oparaeke and Kuhiep, 2006; Panesar
and Shinde, 2011). Different type of anthraquinones, saccarides, vitamins,
essential and nonessential amino acids, enzymes and inorganic compounds are
present in Aloe vera (Vogler and Enst, 1999).
Leaves are the main part, which contains most of these compounds (Okamura
et al., 1997; Okamura et al., 1998;
Vogler and Enst, 1999; Ni et al.,
2004). Locally Aloe vera is known as Kunwarghandel and
is used as an ingredient of herbal formulation used to treat the diabetes (Ahmad
et al., 2009). Rajasekaran and Sathishsekar (2007)
reported that Aloe vera gel extract is potential agent in preventing
the glycoproteins mediated secondary diabetic complications in experimentally
induced diabetic rats. Choi et al. (1996) isolated
aloe-emodin and different form of aloins (aloin A and B) from freeze dried Aloe
vera leaves. Nidiry et al. (2011) also reported
that aloin and aloe-emodin are main constituents of Aloe vera extract.
Perez et al. (2007) studied the effect of aloe
extract containing high concentrations of aloin and aloe-emodin on experimentally
induced insulin resistant mice. They found significant decrease in blood glucose
levels along with protective effect on insulin producing β cells. It can
be concluded that these compounds are major contributors for antidiabetic activity
of Aloe vera. Due to the presence of gibberellin-like active substances
it showed anti-inflammatory activity in diabetic animals (Davis
and Maro, 1989). Protective effects of its extract on β cells make
it more suitable for the treatment of type I diabetes. Pritam
and Kale (2007) stated that a significant decrease in antioxidant activity
of Aloe vera was observed when it was infected with Alternaria alternata.
So before any medicinal use of plant it should be checked for any kind of phyllosphere
Artemisia herba-alba: Artemisia herba-alba commonly known
as white wormwood is a dwarf shrub that usually grows in arid areas. Leaves
of this plant have pungent smell and are covered by woolly hairs (Salido
et al., 2004). Antioxidant properties of this plant are well reported
(Al-Mustafa and Al-Thunibat, 2008). Sterol, terpene and
alcohols have been reported from aerial parts and essential oil of this plant
(Laid et al., 2008; Kalemba
et al., 2002). Aqueous extract of aerial parts administrated at the
rate of 0.39 g kg-1 body weight results in significant reduction
of blood glucose levels in both diabetic rats and rabbits (Al-Shamaony
et al., 1994). Khafagy et al. (1971)
isolated the santonin and stigmasterol from flowering branches of Artemisia
herba alba. Santonin has been banned in USA due to its potential toxicity
(Fadhil, 2008). On administration of stigmasterol in
mice a reduction in blood glucose and an increase in insulin concentration was
observed (Panda et al., 2009). Artemisia herba-alba
is an ingredient of hyponidd (herbomineral formulation) and this formulation
is reported for both antidiabetic and antioxidant activity (Subash-Babu
and Ignacimuthu, 2007). Presence of stigmasterol as an active compound of
this formulation further supports its application as antidiabetic agent. Almasad
et al. (2007) reported the adverse effect of Artemisia herba alba
on reproductive system of female Sprague-Dawley rats.
Catharanthus roseus: Catharanthus roseus L. (G. Don) is
an important medicinal plant of family Apocynaceae (Jaleel
et al., 2009). Its extract showed a considerable wound healing, anti-tumor,
hypotensive and antifungal activity (Nagori and Solanki,
2011; Rana et al., 2004; Ara
et al., 2008; Saravanan and Valluvaparidasan,
2001). It is locally known as Sada bahar and used to deal with
diabetes (Ahmad et al., 2009). Jarald
et al. (2008) proved that leaf extract have more strong antihyperglycaemic
activity as compared to extracts of other plant parts (stem, flower and root).
Habib et al. (2005) also reported hypoglycemic
effect of its leaf extract on normal rats. The aqueous extract of its leaves
at the dose of 5000 mg kg-1 showed significant improvement in different
physiological/histological parameters, which were altered after the onset of
diabetes in streptozotocin induced diabetic rats (Prasad
et al., 2009). Nammi et al. (2003) studied
the effect of leaf juice extract of Catharanthus roseus on blood glucose
levels of alloxan-induced diabetic rabbits. They found strong and long lasting
antidiabetic effect of its extract in comparison with glibenclamide. They further
concluded that its active ingredient might have enhanced the insulin secretion
from β-cells due to which reduction in blood glucose levels was observed
in both diabetic and normal animals. Same hypoglycemic effect was also observed
in streptozotocin induced rats (Ahmed et al., 2007).
Leaves of this plant contain many compounds like chlorogenic acid, kaemferol
trisaccharides, quercetin trisaccharides (Mustafa and Verpoorte,
2007). Chlorogenic acid was found to have hypoglycemic activity in mice
(Nicasio et al., 2005). Flowers of this plant
are also used for treatment of diabetes (Rahmatullah et
al., 2009). Many types of flavonoid (Quercetin, Malvidin, Petunidin,
Hirsutidin) have been reported to be present in its flower (Mustafa
and Verpoorte, 2007). Quercetin (active component of flower) significantly
reduced the plasma glucose levels in streptozocin induced diabetic rats but
showed no effect on normal individuals (Vessal et al.,
2003). This antihyperglycemic effect is attributed to the increased insulin
release as a result of quercetin regenerative effect on pancreatic islets. Siddiqui
et al. (2010) studied the cytotoxicity of Catharanthus roseus
fractions on Human Colorectal Carcinoma Cell Line (HCT 116) and observed a dose
dependent cytotoxic effect.
Cichorium intybu: Cichorium intybu have stalked leaves
with more or less hairy stem and toothed scales (Rose, 1981).
Its extract have shown antihepatotoxic, anti-ulcerogenic and antimicrobial properties
(Hasan et al., 2007; Madani
et al., 2008; Dulger and Gonuz, 2004; Rifat-uz-Zaman
et al., 2006a; Rifat-uz-Zaman et al., 2006b).
Powder obtained from the dried roots of Cichorium intybus (locally known
as Kasni) is used to treat diabetes (Ahmad et
al., 2009). Twenty percent decrease in blood glucose of streptozotocin
induced rats was observed when administrated with ethanolic extract of Cichorium
intybus, but there was no increase in blood insulin concentrations (Pushparaj
et al., 2007). Presence of caffeoylquinic acids and chlorogenic acid
in various part of Cichorium intybus have been reported (Milala
et al., 2009; Mulinacci et al., 2001).
Mulinacci et al. (2001) characterized the chicoric
acid and chlorogenic acid from its leaves. This chicoric acid is reported as
a potential antidiabetic agent with both insulin sensitizing and secretary property
(Tousch et al., 2008; Andrade-Cetto
and Wiedenfeld, 2001). Chlorogenic acid as an antidiabetic agent is useful
for non-insulin-dependent diabetes (Hemmerle et al.,
1997). Inulin (carbohydrate) present in almost all parts of plant (Milala
et al., 2009) is reported to have potential beneficial effects as
an antidiabetic agent against non-insulin-dependent diabetes (Yun
et al., 2009). Quercetin is reported to have significant antidiabetic
activity (Vessal et al., 2003). A variety of quercetins
(quercetin-3-O-glucoside, quercetin-3-O-glucuronide, quercetin-3-O-β-D-glucuronide)
has been reported as phytochemicals of this plant (Mulinacci
et al., 2001; Yang et al., 2009). Some
of these have been analyzed for their antidiabetic activity as quercetin-3-O-glucoside
was reported to have hypoglycemic effect in alloxan induced diabetic rats (Panda
and Kar, 2007).
Citrullus colocynthis: Almost all parts of Citrullus colocynthis
are used for various purposes in Pakistan (Memon et al.,
2003). Antidiabetic, antifungal, antibacterial, hypolipidaemic and local
anesthetic activity of different plant parts extracts have been reported in
various studies (Gurudeeban et al., 2010; Boulenouar
et al., 2009; Hadizadeh et al., 2009;
Thirunavukkarasu et al., 2010; Daradka
et al., 2007; Ramanathan et al., 2011).
Its extract is also used for the synthesis of nanoparticles (Satyavani
et al., 2011b). Extracts of different fruit parts were analyzed for
their insulinotropic effects (Nmila et al., 2000).
All of the tested extracts showed potential insulin secretary activity and authors
concluded that the antidiabetic activity of fruit is due to the presence of
different phytochemicals (β-pyrazol-1-ylalanine) in its seeds. To some
extent aqueous seed extract was found to have positive effect on streptozotocin
induced diabetic rats (Al-Ghaithi et al., 2004).
Isolation of various phytochemicals (alkaloids, flavonoides, glycosides, phenols,
proteins, saponins) have been reported from its fruit (Najafi
et al., 2010; Delazar et al., 2006).
Antihyperglycemic activity of alkaloidal extract was non-significant in normal
rabbits but glycosidic extract showed significant reduction in serum glucose
levels (Abdel-Hassan et al., 2000). Saponin (plant
phytochemical) also showed significant reduction in blood glucose levels in
alloxan induced diabetic rabbits. Although this plant is been used as antidiabetic
remedy but in a study conducted by Wafsi (1994) no effect
of leaves and pulp was observed on glucose levels in diabetic and non-diabetic
rats. High dose of Citrullus colocynthis could induce liver fibrosis
and hepatocyte necrosis when administered in rats and this toxic effect is dose
dependent (Dehghani and Panjehshahin, 2006).
Coriandrum sativum: Coriandrum sativum is locally used
for various purposes in Pakistan (Hamayun et al.,
2005; Hussain et al., 2009). Various reports
have reported its antioxidant and antihyperglycemic activity is well reported
(Sultana et al., 2010; Wagensteen
et al., 2004; Kansal et al., 2011; Gallagher
et al., 2003; Srinivasan, 2005). Its extract
has shown insulin-stimulating activity and there are chances that this activity
is controlled by more than one phyto-constituents of its extract (Gray
and Flatt, 1999). β-carotene is reported as one of the five fractions
of its plant extract (Guerra et al., 2005) and
it was found to be effective in reducing the diabetic complications in alloxan
induced diabetic rats (Aruna et al., 1999).
Cucurbita máxima: Cucurbita máxima are annual
herbaceous vines with yellow flowers having a climbing stem up to 12 m long
(Winkler et al., 2005). It is locally known as
Wun and its fruits are consumes as vegetables in NWFP, Pakistan
(Jan et al., 2009). Saha et
al. (2011) reported that methanol extract of aerial parts successfully
reduced the fasting blood glucose levels in streptozotocin induced Wistar albino
rats (Saha et al., 2011). Its fruit contain beta-carotene
(Muntean and Rotar, 2010), which is a known antidiabetic
compound (Aruna et al., 1999). A range of sterols
(25(27)-dehydroporiferasterol, clerosterol, isofucosterol, stigmasterol, sitosterol,
campesterol and codisterol) and fatty acids are present in its seeds (Garg
and Nes, 1984; Fokou et al., 2009). Stigmasterol,
which is also present in its seeds, is a known hypoglycemic agent (Panda
et al., 2009). But Jamaluddin et al. (1994)
observed no hypoglycaemic activity of stigmasterol when tested without β-sitosterol.
So presence of β-sitosterol in its seeds (Basaran et
al., 1998) further affirms the claim that both compounds stigmasterol
and β-sitosterol contribute towards the hypoglycemic activity of its seed.
Compounds like beta-carotene, stigmasterol and β-sitosterol could be the
major contributing factors for its antidiabetic activity.
Elephantopus scaber: Elephantopus scaber is a stiff, inflexible
and wild perennial herb, 10-50 cm long and usually grows under shady places.
From the ancient times it has been known as a medicinal herb used for the treatment
of several diseases (Wang et al., 2004). It is
reported in many Asian countries including Pakistan (Ho et
al., 2009). Its leaf and root extracts showed significant reduction
in glucose levels of alloxan induce diabetic rats along with a regenerative
effect on islet β-cells (Daisy et al., 2007).
Same effect of its crude extract on serum glucose was observed in addition to
increased insulin concentration in streptozotocin induced hyperglycemic rats
(Jasmine and Daisy, 2007). Mohan et
al. (2010) reported the presence of different steroids in its leaf and
rhizomes extracts. A steroid, 28Nor-22(R)Witha 2,6,23-trienolide isolated from
its acetone extract showed significant antidiabetic activity in streptozotocin
induced diabetic rats (Daisy et al., 2009). Its
regenerative effect on islet β-cells could be the most probable mode of
action for its antidiabetic activity.
Equisetum arvense: Equisetum arvense is locally known
as Chihly and used as herbal remedy to treat different diseases
(Khan and Khatoon, 2008). Safiyeh et
al. (2007a) observed significant decrease in serum glucose levels of
experimentally induced diabetic rats on administration of its extracts. Histological
studies showed that this extract have regenerative effect on pancreas (Soleimani
et al., 2007). Along with its antidiabetic activity its extract also
showed renoprotective activity (Safiyeh et al., 2007b).
Phytochemicals of this herb are mainly categorized as flavonoids, alkaloids,
minerals, phenolic petrosins, triterpenoids, saponins and phytosterols (Sandhu
et al., 2010). Glycation inhibitors are useful in diabetes treatment
as advanced glycation end products (AGEs) are abundantly present in diabetic
people and increase in AGEs are thought to be linked with complication in diabetes
(Nakamura et al., 1997). Quercetin 3-O-β-d-glucopyranoside
is a know glycation inhibitor (Jung et al., 2006)
and it is reported as one of its active phytochemicals (Veit
et al., 1993). Its regenerative effect on pancreas and glycation
inhibition action could be the most probable mode of action for its hypoglycemic
Momordica charantia: The immunostimulant, antidiabetic and anticancer
properties of its extract are well reported (Prasad et
al., 2006; Rahman et al., 2005; Tanaka
et al., 2009; Asiamah et al., 2011).
For successful treatment of diabetes people use fresh juice or powder of Momordica
charantia (Ahmad et al., 2009; Fatima
et al., 2004). Leaf methanolic extract of Momordica charantia
has shown mild hypoglyceamic effect on alloxan induced diabetic rats (Ataman
et al., 2006). In another study its fruit methanolic extract has
shown dose dependent hypoglycemic and antihyperglycemic effect in normal and
diabetic rats, respectively (Kolawole et al., 2011).
Seed aqueous extract significantly restored the altered enzymatic activities
in streptozotocin induced diabetic rats (Sathishsekar and
Rajasekaran, 2007). Srivastava et al. (1993)
tested the hypoglycemic activity of both aqueous extract and dried powder of
fruit on alloxan induced diabetic rats. They found significant decrease in blood
glucose levels after three weeks on administration of aqueous extract but hypoglycemic
effect of dried fruit powder was not significant. Fruit extract also showed
enhanced insulin secretion from islets of langerhans and restored its histological
architecture in alloxan induced diabetic rats (Fernandes
et al., 2007). Ullah et al. (2011) reported
that bitter gourd contain phytochemicals like tannin, flavonoids, terpenoids,
cardiac glycosides, triterpin and sterol, resin, amino acid and phenolic compounds.
Harinantenaina et al. (2006) identified two triterpene
(5β,19-epoxy-3β,25-dihydroxycucurbita-6,23(E)-diene and 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al)
as major compounds of dried fruit methanolic extract. Both of these compounds
showed hypoglycemic effects in experimentally induced diabetic mice. A polypeptide
(p-insulin) isolated from Momordica charantia fruit effectively lowered
the serum glucose levels in gerbils, langurs and humans (Khanna
et al., 1981; Raman and Lau, 1996). Caffeic
acid was identified as one of the phenolic compounds isolated from Momordica
charantia extract (Kubola and Siriamornpun, 2008).
It is reported that under diabetic conditions the Glucose-6-phosphatase expression
increases significantly (Liu et al., 2008). This
catechin compound has down-regulatory effect on glucose-6-phosphatase expression
(Abe et al., 2009). Shin et
al. (2009) correlated the presence of catechin in green tea with its
activity in reducing the risk of type 2 diabetes. Tan et
al. (2008) isolated four cucurbitane glycosides and concluded that these
compounds could be used as potential agents to treat diabetes and obesity. Khan
and Anderson (2003) reported that its dried seed have insulin potentiating
activity. In another study Hamid et al. (2008)
reported that its methanolic extract have shown high insulinotrophic activity
among 14 tested plants. But Srinivasan and Karundevi (2005)
did not find any change in plasma insulin levels after administration of its
aqueous seed extract on alloxan induced diabetic rats. This could be due to
the variation in method used to obtain its aqueous extract. Ataman
and Idu (2007) reported that on parenteral administration of Momordica
charantia leaf extract, its long-term use should be avoided as it may have
hazardous effects on liver.
Murraya koenigii: Murraya koenigii is a herbal plant and sometimes
also called spreading shrub when it grows up to 2.5 m. This plant is widely
used in spices and condiments but leaves of this plant are used as flavoring
agent and folk medicine for the treatment of various diseases (Tembhurne
and Sakarkar, 2010). Insecticidal activity of its crude extract to Sitophilus
oryzae and Tribolium castaneum is recently reported (Rani
and Devanand, 2011). Aqueous extract of this plant showed significant decrease
in blood glucose levels in both diabetic and non-diabetic rabbits, in addition
its extract also showed improvement in glucose tolerance (Kesari
et al., 2005). Kesari et al. (2007)
analyzed the aqueous leaves extract activity in severe diabetic rats and found
it effective in bringing down the severity level of disease. Arulselvan
and Subramanian (2008) analyzed the effect of ethanolic leaf extract of
Murraya koenigii on streptozotocin induced diabetic rats. They observed
restoration of altered enzymatic and non-enzymatic antioxidant activities in
liver and serum glucose and insulin levels. Arulselvan et
al. (2006) reported the insulin stimulatory activity of its extract
in experimentally induced diabetic rats. It is thought that its protective effects
on pancreatic β-cells and antioxidant activity are major factors that contribute
towards its hypoglycemic activity (Arulselvan and Subramanian,
2007). Improvement in glucose tolerance, insulin stimulatory activity and
protective effect on pancreatic β-cells all in combination contribute towards
its anti-hyperglycemic activity.
Ocimum sanctum: Ocimum sanctum (Tulsi) is an aromatic
herb having stem trailing along the ground with 3-foliate leaves (Rahman
et al., 2010). This plant is famous for its medicinal value and used
for various purposes to deal infectious wounds, cancer, as a antioxidant, anti
neoplastic and anti-tuberculosis (Raghavendra et al.,
2006; Hemalatha et al., 2011; Misra
et al., 2006; Islam et al., 2011; Farivar
et al., 2006). Some studies have reported insecticidal, nematicidal
and antimicrobial activity of its extract (Vinayagam
et al., 2008; Bharadwaj and Sharma, 2007; Rahman
et al., 2010; Mishra and Mishra, 2011). Its
extract also showed some developmental effects on fish immunity (Pavaraj
et al., 2011). Same effect was observed in chicken when treated with
a herbal mixture containing Ocimum sanctum as one of its herbal ingredient
(Oyagbemi et al., 2008). Grounded leaves of Ocimum
sanctum (locally known as Tulsi) with Ocimum album is
used by local people for treatment of diabetes (Ahmad et
al., 2009). Alcoholic extract of its leaves significantly decreases
the blood glucose levels of alloxan induced diabetic rats (Vats
et al., 2002). Hussain et al. (2001)
found that aqueous extract of Ocimum sanctum successfully reduced the
fasting blood glucose and improved the glucose tolerance in streptozotocin induced
diabetic rats. Its leaf powder showed both hypolipidemic and antihyperglycemic
effects when fed to diabetic rats for one-month period (Rai
et al., 1997). On administration of Ocimum sanctum extract
a decrease in plasma glucose was observed in addition to an increase in liver
and kidney weight in streptozotocin induced diabetic rats (Vats
et al., 2004). Joshi et al. (2011)
reported the presence of anthocyanins in aqueous ethanolic extract of Ocimum
sanctum and these anthocyanins act as stimulant for beta-cells to secrete
insulin (Jayaprakasam et al., 2005).
Phyllanthus amarus: Phyllanthus amarus is a widely distributed
pantropical weed usually grows under moist and shady places. Its stem leaves
and seeds are extensively used for medicinal purposes (Khan
et al., 2011; Costa et al., 2006; Idu
and Onyibe, 2007; Annamalai and Lakshmi, 2009; Joseph
and Raj, 2011). This plant is used in Dir Kohistan valleys (NWFP) as a herbal
medicine (Jan et al., 2009). Alkaloids, flavonoids,
terpenoids, saponins, tanins, steroids and cardiac glycosides are the active
phytochemicals of this plant (Bankole et al., 2011).
Srividya and Periwal (1995) found that it has hypoglycemic
effect on treated group of humans. This plant showed antidiabetic activity both
in insulin dependent and non-insulin dependent diabetic rats (Bavarva
and Narasimhacharya, 2007). Mice treated with its aqueous and seed extracts
showed a dose dependent decrease in plasma glucose, cholesterol and weights
(Adeneye et al., 2006). Compounds inhibiting the
activity of enzymes (α-glucosidase, α-amylase), that are involved
in carbohydrate digestion are considered as potential antidiabetic agents (Tadera
et al., 2006). Ali et al. (2006) examined
the α-amylase inhibitory activity of Phyllanthus amarus hexane extract
and identified the mixture of oleanolic aicd and ursolic acid as potential α-amylase
inhibitory compounds. Oleanolic acid showed hypoglycemic effect along with increase
in weight and serum insulin levels of streptozotocin induced diabetic rats (Dawei
et al., 2007). Ursolic acid showed a preservative effect on pancreatic
β-cells in experimentally induced type 1 diabetic mice, as a result there
was increase in insulin levels, which ultimately resulted in the reduction in
plasma glucose levels (Jang et al., 2009). Chattopadhyay
et al. (2006) reported its regenerative effect on liver and in another
study an increased insulin activity is also reported after the administration
of its hydroalcholic extract in partially hepatectomised albino rats (Chattopadhyay
et al., 2007). Careful use of P. amarus has been recommended
by Adedapo et al. (2005) as some of its fractions
had toxic effect on rat serum. All these finding conclude that inhibition of
α-amylase enzyme and protective effect on β-cells may be the potential
mode of action of Phyllanthus amarus against diabetes.
Semecarpus anacardium: This plant is known for its therapeutic
and antimicrobial properties (Veena et al., 2006;
Sharma et al., 2010). Ethanolic extract of dried
nuts showed significant antihyperglycemic effect in normal and experimentally
diabetic rats (Kothai et al., 2005; Arul
et al., 2004). Its nut milk extract showed hypoglycemic activity
along with increase in body weight and serum insulin levels in streptozotocin
induced diabetic rats (Jaya et al., 2010). Nut
shells mainly contain biflavonoids and oil of nuts contains a mixture of phenolic
compounds, oleic acid, linoleic acid, palmitic acid, stearic acid and arachidic
acid (Majumdar et al., 2008; Aseervatham
et al., 2011). A mixture of isomeric forms of linoleic acid (a constituent
of kernel oil) has hypoglycemic effect due to their insulin stimulating activity
(Ryder et al., 2001). Ascorbic acid (a phytochemical
of its kernel oil) helps to reduce the arterial stiffness in type 2 diabetic
patients (Mullan et al., 2002). Phytochemical
linoleic acid could be responsible for its main antidiabetic activity and presence
of ascorbic acid makes it suitable to deal with diabetes related complications.
Silybum marianum: Silybum marianum is a very old herbal
remedy, now a days it is used as anticancer, antidiabetic, cardioprotective
and for many other purposes (Tamayo and Diamond, 2007;
Nobakht et al., 2011). Hepatoprotective effects
of this plant are well reported (Hasanloo et al., 2005;
Madani et al., 2008; Dehghan
et al., 2010). Maghrani et al. (2004)
concluded that extract of aerial parts of Silybum marianum have antidiabetic
effect on streptozotocin induced diabetic rats. Its extract was also found to
be useful against diabetic nephropathy in streptozotocin diabetic rats (Vessal
et al., 2010). Huseini et al. (2006)
studied the effect of Silybum marianum seed extract on fifty one type
2 diabetic patients and recorded an overall improvement in glycemic profile
of patients. The use of this palnt may help in the reduction of diabetes related
Trigonella foenum-graecum: Trigonella foenum-graecum L.
(localy known as Maithi) is a leafy vegetable widely grown in NWFP Pakistan
(Marwat et al., 2009). Many authors have reported
antimicrobial, anti-inflammatory, antioxidant, antihyperlipidemic and other
beneficial medicinal activities of its plant extract (Bonjar,
2004; Subhashini et al., 2011; Semalty
et al., 2009; Mohamed and Metwally, 2009;
Al-Sobayil, 2008; Semalty et al.,
2010; Premanath et al., 2011; Bahram
et al., 2005). Useful application of its seeds in poultry are also
reported (Abbas, 2010). Seeds and leaves of this plant
are used for medicinal purposes including diabetes. Trigonella foenum graecum
seed powder successfully lowered the plasma glucose levels and brings the altered
enzymatic levels to normal values in alloxan-induced diabetic rats (Raju
et al., 2001). Fowden et al. (1973)
reported the isolation of 4-Hydroxyisoleucine from the seeds of Trigonella
foenum-graecum. This amino acid showed glucose dependent insulin secreting
activity (Sauvaire et al., 1998). Broca
et al. (2004) concluded that this amino acid could improve the insulin
sensitivity. In type II diabetic rats this compound showed insulin stimulating
effect on pancreatic beta cells (Broca et al., 1999).
Its antioxidant antihyperlipidemic, insulin secreatary activity and reported
positive effect in type 2 diabetes prove its sifnificant effects as an antidiabetic
Zingiber officinale: Zingiber officinale is a perennial
herb, having one meter long erected stem and possesses tuberous rhizomes that
are used as a spice in cooking throughout the world. Ginger plant bears purple
flowers and there are some essential oils present in it, which provides good
aroma to the spice (Malu et al., 2009). Its local
name is Adrak and grown on large scale in different parts of NWFP, it is used
as herbal medicine to treat a range of diseases (Marwat et
al., 2009; Ene et al., 2008; Akram
et al., 2011). Antibacterial, antimicrobial, nephroprotective, antioxidant
and hepatoprotective activity of its extract is well documented (Adebolu
et al., 2007; Neogi et al., 2007; Patrick-Iwuanyanwu
et al., 2007; Harliansyah et al., 2007;
Prakash et al., 2008; Sunilson
et al., 2009; Abeer Waggas, 2009; Lakshmi
and Sudhakar, 2010). Extract of Zingiber officinale is also reported
to have nematicidal and mosquitocidal activity (Hassan et
al., 2001; Dadji et al., 2011). It is
also reported as beneficial component of poultry feed (Herawati,
2010). Volatile oils, tanins, alkaloids saponins and flavonoids are reported
as its active phytochemicals (Hashemi et al., 2008).
The juice of Z. officinale showed antidiabetic action in alloxan induced
diabetic rats (Asha et al., 2011). Raw ginger
extract at the rate of 500 mg kg-1 in streptozotocin induced diabetic
rats showed potential antihyperglycemic, hypocholesterolaemic and hypolipidemic
activity (Al-Amin et al., 2006). Its juice significantly
reduced the fasting glucose levels and increased the insulin levels in streptozotocin
induced type I diabetic rats (Akhani et al., 2004).
A compound named as 6-Gingerol is reported by Johji et
al. (1988) as an active constituent of ginger. For the treatment of
type 2 diabetes this (6)-gingerol is reported as a potential antidiabetic, lipid
lowering and antioxidant agent (Singh et al., 2009).
Adanlawo and Dairo (2007) reported that its extract have
not shown and harmful effects on different parts of albino Wistar rats. So the
presence of (6)-gingerol and its reported potential to treat the type I diabetes
make it suitable for both type I and type II diabetes.
DISCUSSION AND CONCLUSION
There are many factors which are critical in the development of diabetes. Decline
of antioxidant defense mechanism along with high levels of free radicals (formed
as a result of glucose oxidation and nonenzymatic glycation of proteins) generate
an oxidative stress on patient (Maritim et al., 2003).
This oxidation stress lead to the damage of cellular organelles, enzymes, increased
lipid peroxidation and development of insulin resistance. Some herbal plants
(A. cepa, A. sativum, C. sativum, O. sanctum, T. foenum-graecum and Z. officinale)
have been reported for their antioxidant properties. Use of antioxidnats reduce
the antioxidant stress and improve diabetes (Rahimi et
al., 2005) therefore herbal plants (with antioxidant activities) could
decrease the harmful effects of free radicals. Herbs and herbal drugs act through
different ways to reverse the diabetic complications. For example Urtica
dioica is useful for the treatment of diabetes and its affects thorugh pancreatic
and extra pancreatic pathways (Mehri et al., 2011).While
Phlomis anisodonta control diabetes by increasing insulin level and combating
oxidative stress through activation of hepatic antioxidant enzymes (Sarkhail
et al., 2007). In support of our results that most of studied herbs
act through antioxidant mechanism is Hasani-Ranjbar et
al. (2008) who have listed herbal medicines which are safe against obesty
as reported in this study that most of studied herbs have antioxidant effects.
There are about 70% of diabetic patients, which suffer with hypertension (Dodson,
2002). Hypertension increases the risk of retinopathy, nephropathy and peripheral
vascular disease in diabetic patient (Sowers et al.,
1998). Three herbs out of 19 are reported for their anti-hypertension activities
which are A. cepa, A. sativum and C. roseus. Lipid profile is
also important in diabetic patient as with successful serum lipid control the
risk for cardiovascular complications can be reduced in diabetic patient (Deshpande
et al., 2008). In type 1 diabetes inflammation have negative effect
on beta-cells function and strengthen the immune system against beta-cell destruction
(Eizirik et al., 2009). Inflammatory cytokines
such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β and
free radicals are believed to play key roles in destruction of pancreatic β
cells while Silybum marianum seed extract reduced levels of inflammatory
cytokines such as TNF-α and IL-1β and oxidative stress mediators (Malihi
et al., 2009) O. sanctum and T. foenum-graecum both
have antiinflammatory and antilipidemic activity, these two herbs can be employed
to overcome these complication in diabetic patients. Some herbs are reported
to have protective or regenerative effect on insulin producing beta-cells or
liver (A. vera, E. scaber, M. koenigii, O. sanctum, P. amarus, S. marianum,
T. foenum-graecum and Z. officinale). These herbs can be employed
for treatment of type 1 diabetes. S. marianum, M. charantia and C.
intybus are reported for their specific antidiabetic activity in type 2
diabetes. P. amarus and Z. officinale are reported for antidiabetic
activity in both type 1 and type 2 diabetes. Toxicity of herbal plants should
be studied as toxic effects of some herbs (A. cepa, A. sativum, A. herba-alba,
C. roseus, C. colocynthis, M. charantia) have been reported. So time and
duration of dose should be chosen carefully to avoid any harmful effect of applied
herb. On the basis of reviewed literature four herbs O. sanctum, Z. officinale,
T. foenum-graecum and P. amarus were found to be most effective in dealing
with diabetes and its related complication. Inclusion of these herbs in daily
food routine may help to reduce the prevalence of disease Pakistan.
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