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Comparative Evaluation Of Anti-Hyperglycemic Effect Of Herbal Medicinal Plants Extracts On Alloxan Induced Diabetic Albino Rats

By: Sonia Aziz (2011-VA-03) | Ms. Asma Waris.
Contributor(s): Ms. Faiza Masood | Dr. Maryam Javed.
Material type: materialTypeLabelBookPublisher: 2014Description: 55p.Subject(s): Department of BiochemistryDDC classification: 2209,T Dissertation note: Diabetes mellitus is a clinical syndrome described as inappropriate hyperglycemia triggered by a relative or absolute deficiency of insulin or by a resistance to the action of insulin at the cellular level. It is the most shared endocrine disorder, upsetting 16 million individuals in the United States and as many as 200 million worldwide (Debra, 1991). The word diabetes was devised by the Greek physician Aeretaeus in the first century A.D. In the 17th century, Willis detected that the urine of diabetics as ideally sweet as if infused with honey or sugar. The existence of sugar in the urine of diabetics was established by Dobson in 1755 (Straton et al. 2000). Diabetes mellitus is a global health crisis, which has been obstinately disturbing the humanity, regardless of the socioeconomic profile and geographic location of the population. According to an estimate, one person is identified with diabetes every 5s somewhere in the world, while someone dies of it every 10s. Diabetes mellitus has achieved a pandemic form. Hence, it is very vital to control diabetes and its difficulties to lessen the human suffering (Wild et al. 2004). Alloxan a glucose equivalent and is toxic by selectively abolishing insulin-producing cells in the pancreas (that is beta cells) of many animal species. This produces an insulin-dependent diabetes mellitus (called "Alloxan Diabetes") in these animals, with features similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially amasses in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, produces reactive oxygen species which start toxicity by its redox reaction (Lenzen et al. 1998). There are diverse methods to the management of diabetes, like insulin treatment in type 1 diabetes: Sulphonylureas, which discharge insulin from pancreas by blocking the ATP-sensitive potassium channels; Biguanides, which reduce the insulin resistance; Thizaolidinediones, which upsurge the insulin sensitivity; alpha-glucodase inhibitors like acarbose, which lessen glucose absorption from intestine, thus reducing postprandial hyperglycemia; metiglinides like repaglimide and nateglamide, which are insulin secretogogues (Aslam, 1988). In spite of the statistic that synthetic drugs such as insulin, investigators have been building efforts to find insulin-like substances from plant sources for the treatment of diabetes. More than 1200 plant species have been suggested for the managementof diabetes (Radha et al. 2011) Natural resources such for example plants are cherished source of bioactive compounds. A large number of drugs have been recognized in medicinal practice from natural products (Philipeon et al. 2010). Recent scientific research and clinical studies have established the usefulness of some medicinal plants and herbal preparations in the development of standard glucose homeostasis. Herbal treatment have been used in patients with insulin-dependent and non-insulin dependent diabetes, diabetic retinopathy, diabetic peripheral neuropathy and other penalties of this metabolic disease (Ahmed et al. 2006). The herbal drugs are recommended extensively because of their effectiveness, less side effects and comparatively low cost (Lezney et al. 2004). Ethno pharmacological reviews show that more than 1200 plants are used in customary medical systems for their suspected hypoglycemic activity (Marles and Farnsworth, 1995, Dey et al. 2002, Grover et al. 2002). The hypoglycemic activity of a huge number of these plants/plant products has been appraised and inveterated in animal models (Gupta et al. 2005, Kesari et al. 2006) as well as in human beings (Herrera et al. 2004, Jayawardena et al. 2005). In some circumstances the bioactive principles have also been secluded and identified. However, the mechanism of action whereby most of these plants and yields lesser the blood glucose level rests hypothetical. This study reveals the comparative effect of different herbal plants effect on alloxan induced diabetic rats. Six different herbal plants have been used in this study to investigate the hypoglycemic activity. These plants areAllium sativum (Garlic), Aloe vera(Kanwargandal), Gymnemasylvestre (Gurmar), Momordicacharantia (karela), Trigonellafoenum-graecum (Methidana), and Syzigiumcumini(Jamun). Table 1: Plants used in present study Plant and family Plant part used Active ingredient Mechanism of action Reference Allium sativum, Alliaceae Garlic gloves S-methyl cysteine sulphoxide-precursor of allicin and garlic oil Arouse in vitro insulin discharge,Hinder glucose making by the liver Sheela et al. 1992, Augusti and Shella 1996. Aloe vera, Aspholedeceae Leaf pulp Phytosterols Excite production or discharge of insulin Modify action of carbohydrate processing enzymes Rajasekaran et al. 2004, Tanaka et al. 2006. GymnemaSylvestre, Asclepiadaceae Leaves Gymnemosides and gymnemic acid (from the saponin fraction) Triterpene glycosides Kindle exudation of insulin from rat islets. Declines the activity of gluconeogenicenzymes,Induce beta cell regeneration. Shanmugasundaram, 1990, Chattopadhyay, 1999. Mormordicacharrantia, Cucurbitaceae Fruit pulp Charantin (a peptide),Insulin like polypeptide P ("vegetable insulin") Encourage insulin secretion, Quash the activities of gluconeogenic enzymes Rises the quantity of beta cells in diabetic rats Rao et al. 1981, Day et al. 1992, Sarkar et al. 1996. Trigonellafoenumgraecum, Fabaceae Seeds  Alkaloid-trigonelline, nicotinic acid, and coumarin  4hydroxyisoleucine Galactomannan depress digestion and absorption of carbohydrates Upsurge glucose induced insulin release Khosla et al. 1995, Hannan et al. 2007. Syzigiumcumini Seeds  Mycaminose Kindle kinases intricate in peripheral utilization of glucose  Achrekar et al. 1992.  Kumar et al. 2008 1.1: Allium sativum(Garlic) is a common zesty flavoring agent used since prehistoric times. Garlic has been cultured in all over world for its distinctive flavor, foodstuff, and medicinal properties. It has mostly been ascribed to its hypoglycemic, anticoagulant, antibiotic, hypo-cholesterolaemic, antihepatotoxic, anticancer, immune system modulatory and antioxidant possessions (Bakri and Douglas, 2005). Figure 1: structure of allicin 1.2: Aloe vera(Kanwargandal)is one of the therapeutic plants which are conventionally well accredited plant in the controlling of diabetes. It fits to family Liliaceae (sub-family of the Asphodelaceae). Many studies titles that the high innards of phenolic compounds, glycosides (aloins), 1,8-dihydroxyanthraquinone derivatives,β -1,4 acetylated mannan, mannose-phosphate and alprogenglucoprotein in the A. vera is vital for its biotic action. Through past two years, Aloe vera used as helpful beneficial agent which defensively act as a free radical scavenging and other antioxidant characteristics on diabetic patients, by monitoring raised anions in an alloxan or STZ-induced diabetic animal models (Nakamura, et al. 2011). Figure 2: structure of phytosterole 1.3: Gymnemasylvestre (Gurmar) is a plant used in Asia as a usual cure for diabetes or “sweet urine.” The hypoglycemic action of Gymnema leaves was first recognized in the late 1920s. Gymnema is testified to upsurge glucose uptake and utilization. It also mends the utility of pancreatic β-cells and may also decline glucose captivation in the gastrointestinal tract. Phytochemically the plant has been described to comprehend gymnemagenin- the sapogenin. Gymnemic acid was sequestered in pure states from the hot water extract of leaves of G. sylvestre (Puratchimani and Jha, 2004). Figure 1: structure of gymnemic acid 1.4: Momordicacharantia (Bitter Melon) also known as karela, is one of the plants normally used for its glucose-lowering properties (Ahmed et al., 1998). The slices of the plant usually used contain the entire plant, its fruit or seeds, all of which are bitter due to the manifestation of the chemical momordicin. The anti-diabetic constituents in bitter melon comprise charantin, vicine, polypeptide-p, alkaloids and other non-specific bioactive components such as anti-oxidants (Beloin, et al. 2005). Figure 4: structure of momordicin 1.5: Trigonellafoenum-graecum (Fenugreek L. Leguminosae) is one of the ancient therapeutic plants, originating in India and Northern Africa.The leaves and seeds, which ripe in long pods, are used to formulate extracts or powders for medicinal use.The hypoglycemic properties of fenugreek have been recognized to numerous mechanisms.The amino acid 4-hydroxyisoleucine in fenugreek seeds amplified glucose-induced insulin release in human and rat pancreatic islet cells. Fenugreek seeds apply hypoglycemic effects by exciting glucose-dependent insulin discharge from pancreatic beta cells, as well as by impeding the actions of alpha-amylase and sucrase, two duodenal enzymes involved in carbohydrate breakdown (Gupta, et al. 2001). Figure 5: structure of 4-hydroxyisolucine 1.6: Syzigiumcumini(Jamun) tree belongs to the Myrtaceae family. This is also called as Jamun, Jambul and Jambol in Pakistan, India and Malaya. The barks, leaves and seeds extracts of SC have been testified to have anti-hyperglycemic, anti-inflammatory, antibacterial and anti-diarraheal effects. A complex mycaminose is extracted from its seeds which display anti-diabetic characteristic (WL Li, et al. 2004). Figure 6: structure of mycaminose There are numerous potential mechanisms through which these herbs can perform to regulate the blood glucose level (Tanira, 1994). The mechanisms of action can be associated, commonly to the capability of the plant in question (or its active principle) to lesser plasma glucose level by meddling with one or more of the procedures involved in glucose homeostasis. The described mechanisms whereby herbal antidiabetic remedies decrease blood glucose levels are more or less alike to those of the artificial oral hypoglycemic drugs and are abridged as follows (Acharya et al. 2008, Bastaki, 2005, Bnouham et al. 2006). i) Stimulation of insulin production and/or discharging from pancreatic beta-cells ii) Revival of impaired pancreatic beta cells iii) Development of insulin sensitivity iv) Imitating the action of insulin v) Modification of the action of some enzymes that are tangled in glucose metabolism reducing the absorption of carbohydrates from the gut. The effectiveness of herbal drugs is substantial and they have insignificant side effects than the synthetic antidiabetic drugs. There is growing demand by patients to use the natural products with antidiabetic activity. In recent times there has been improved concern in the plant remedies. Plants grasp certain potentials in the organization of Diabetes mellitus. Isolation and documentation of active ingredients from these plants, preparation of unvarying dose and dosage schedule can play a noteworthy role in improving the hypoglycemic action (Jung et al. 2006).
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Diabetes mellitus is a clinical syndrome described as inappropriate hyperglycemia triggered by a relative or absolute deficiency of insulin or by a resistance to the action of insulin at the cellular level. It is the most shared endocrine disorder, upsetting 16 million individuals in the United States and as many as 200 million worldwide (Debra, 1991).
The word diabetes was devised by the Greek physician Aeretaeus in the first century A.D. In the 17th century, Willis detected that the urine of diabetics as ideally sweet as if infused with honey or sugar. The existence of sugar in the urine of diabetics was established by Dobson in 1755 (Straton et al. 2000).
Diabetes mellitus is a global health crisis, which has been obstinately disturbing the humanity, regardless of the socioeconomic profile and geographic location of the population. According to an estimate, one person is identified with diabetes every 5s somewhere in the world, while someone dies of it every 10s. Diabetes mellitus has achieved a pandemic form. Hence, it is very vital to control diabetes and its difficulties to lessen the human suffering (Wild et al. 2004).
Alloxan a glucose equivalent and is toxic by selectively abolishing insulin-producing cells in the pancreas (that is beta cells) of many animal species. This produces an insulin-dependent diabetes mellitus (called "Alloxan Diabetes") in these animals, with features similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially amasses in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, produces reactive oxygen species which start toxicity by its redox reaction (Lenzen et al. 1998).
There are diverse methods to the management of diabetes, like insulin treatment in type 1 diabetes: Sulphonylureas, which discharge insulin from pancreas by blocking the ATP-sensitive potassium channels; Biguanides, which reduce the insulin resistance; Thizaolidinediones, which upsurge the insulin sensitivity; alpha-glucodase inhibitors like acarbose, which lessen glucose absorption from intestine, thus reducing postprandial hyperglycemia; metiglinides like repaglimide and nateglamide, which are insulin secretogogues (Aslam, 1988).
In spite of the statistic that synthetic drugs such as insulin, investigators have been building efforts to find insulin-like substances from plant sources for the treatment of diabetes. More than 1200 plant species have been suggested for the managementof diabetes (Radha et al. 2011) Natural resources such for example plants are cherished source of bioactive compounds. A large number of drugs have been recognized in medicinal practice from natural products (Philipeon et al. 2010).
Recent scientific research and clinical studies have established the usefulness of some medicinal plants and herbal preparations in the development of standard glucose homeostasis. Herbal treatment have been used in patients with insulin-dependent and non-insulin dependent diabetes, diabetic retinopathy, diabetic peripheral neuropathy and other penalties of this metabolic disease (Ahmed et al. 2006). The herbal drugs are recommended extensively because of their effectiveness, less side effects and comparatively low cost (Lezney et al. 2004).
Ethno pharmacological reviews show that more than 1200 plants are used in customary medical systems for their suspected hypoglycemic activity (Marles and Farnsworth, 1995, Dey et al. 2002, Grover et al. 2002). The hypoglycemic activity of a huge number of these plants/plant products has been appraised and inveterated in animal models (Gupta et al. 2005, Kesari et al. 2006) as well as in human beings (Herrera et al. 2004, Jayawardena et al. 2005). In some circumstances the bioactive principles have also been secluded and identified. However, the mechanism of action whereby most of these plants and yields lesser the blood glucose level rests hypothetical.
This study reveals the comparative effect of different herbal plants effect on alloxan induced diabetic rats. Six different herbal plants have been used in this study to investigate the hypoglycemic activity. These plants areAllium sativum (Garlic), Aloe vera(Kanwargandal), Gymnemasylvestre (Gurmar), Momordicacharantia (karela), Trigonellafoenum-graecum (Methidana), and Syzigiumcumini(Jamun).
Table 1: Plants used in present study
Plant and family Plant part used Active ingredient Mechanism of action Reference
Allium sativum, Alliaceae Garlic gloves S-methyl cysteine sulphoxide-precursor of allicin and garlic oil Arouse in vitro insulin discharge,Hinder glucose making by the liver Sheela et al. 1992, Augusti and Shella 1996.
Aloe vera, Aspholedeceae Leaf pulp Phytosterols Excite production or discharge of insulin Modify action of carbohydrate processing enzymes Rajasekaran et al. 2004,
Tanaka et al. 2006.
GymnemaSylvestre,
Asclepiadaceae Leaves Gymnemosides and gymnemic acid (from the saponin fraction)
Triterpene glycosides Kindle exudation of insulin from rat islets.
Declines the activity of gluconeogenicenzymes,Induce beta cell regeneration. Shanmugasundaram, 1990,
Chattopadhyay, 1999.
Mormordicacharrantia,
Cucurbitaceae Fruit pulp Charantin (a peptide),Insulin like polypeptide P ("vegetable insulin") Encourage insulin secretion,
Quash the activities of gluconeogenic enzymes
Rises the quantity of beta cells in diabetic rats Rao et al. 1981,
Day et al. 1992,
Sarkar et al. 1996.

Trigonellafoenumgraecum,
Fabaceae
Seeds
 Alkaloid-trigonelline,
nicotinic acid, and coumarin
 4hydroxyisoleucine
Galactomannan depress digestion and absorption of carbohydrates
Upsurge glucose induced insulin release Khosla et al. 1995,
Hannan et al. 2007.

Syzigiumcumini Seeds  Mycaminose Kindle kinases intricate in peripheral utilization of glucose  Achrekar et al. 1992.
 Kumar et al. 2008


1.1: Allium sativum(Garlic) is a common zesty flavoring agent used since prehistoric times. Garlic has been cultured in all over world for its distinctive flavor, foodstuff, and medicinal properties. It has mostly been ascribed to its hypoglycemic, anticoagulant, antibiotic, hypo-cholesterolaemic, antihepatotoxic, anticancer, immune system modulatory and antioxidant possessions (Bakri and Douglas, 2005).
Figure 1: structure of allicin

1.2: Aloe vera(Kanwargandal)is one of the therapeutic plants which are conventionally well accredited plant in the controlling of diabetes. It fits to family Liliaceae (sub-family of the Asphodelaceae). Many studies titles that the high innards of phenolic compounds, glycosides (aloins), 1,8-dihydroxyanthraquinone derivatives,β -1,4 acetylated mannan, mannose-phosphate and alprogenglucoprotein in the A. vera is vital for its biotic action. Through past two years, Aloe vera used as helpful beneficial agent which defensively act as a free radical scavenging and other antioxidant characteristics on diabetic patients, by monitoring raised anions in an alloxan or STZ-induced diabetic animal models (Nakamura, et al. 2011).
Figure 2: structure of phytosterole


1.3: Gymnemasylvestre (Gurmar) is a plant used in Asia as a usual cure for diabetes or “sweet urine.” The hypoglycemic action of Gymnema leaves was first recognized in the late 1920s. Gymnema is testified to upsurge glucose uptake and utilization. It also mends the utility of pancreatic β-cells and may also decline glucose captivation in the gastrointestinal tract. Phytochemically the plant has been described to comprehend gymnemagenin- the sapogenin. Gymnemic acid was sequestered in pure states from the hot water extract of leaves of G. sylvestre (Puratchimani and Jha, 2004).
Figure 1: structure of gymnemic acid

1.4: Momordicacharantia (Bitter Melon) also known as karela, is one of the plants normally used for its glucose-lowering properties (Ahmed et al., 1998). The slices of the plant usually used contain the entire plant, its fruit or seeds, all of which are bitter due to the manifestation of the chemical momordicin. The anti-diabetic constituents in bitter melon comprise charantin, vicine, polypeptide-p, alkaloids and other non-specific bioactive components such as anti-oxidants (Beloin, et al. 2005).
Figure 4: structure of momordicin

1.5: Trigonellafoenum-graecum (Fenugreek L. Leguminosae) is one of the ancient therapeutic plants, originating in India and Northern Africa.The leaves and seeds, which ripe in long pods, are used to formulate extracts or powders for medicinal use.The hypoglycemic properties of fenugreek have been recognized to numerous mechanisms.The amino acid 4-hydroxyisoleucine in fenugreek seeds amplified glucose-induced insulin release in human and rat pancreatic islet cells. Fenugreek seeds apply hypoglycemic effects by exciting glucose-dependent insulin discharge from pancreatic beta cells, as well as by impeding the actions of alpha-amylase and sucrase, two duodenal enzymes involved in carbohydrate breakdown (Gupta, et al. 2001).

Figure 5: structure of 4-hydroxyisolucine

1.6: Syzigiumcumini(Jamun) tree belongs to the Myrtaceae family. This is also called as Jamun, Jambul and Jambol in Pakistan, India and Malaya. The barks, leaves and seeds extracts of SC have been testified to have anti-hyperglycemic, anti-inflammatory, antibacterial and anti-diarraheal effects. A complex mycaminose is extracted from its seeds which display anti-diabetic characteristic (WL Li, et al. 2004).
Figure 6: structure of mycaminose

There are numerous potential mechanisms through which these herbs can perform to regulate the blood glucose level (Tanira, 1994). The mechanisms of action can be associated, commonly to the capability of the plant in question (or its active principle) to lesser plasma glucose level by meddling with one or more of the procedures involved in glucose homeostasis. The described mechanisms whereby herbal antidiabetic remedies decrease blood glucose levels are more or less alike to those of the artificial oral hypoglycemic drugs and are abridged as follows (Acharya et al. 2008, Bastaki, 2005, Bnouham et al. 2006).
i) Stimulation of insulin production and/or discharging from pancreatic beta-cells
ii) Revival of impaired pancreatic beta cells
iii) Development of insulin sensitivity
iv) Imitating the action of insulin
v) Modification of the action of some enzymes that are tangled in glucose metabolism reducing the absorption of carbohydrates from the gut.
The effectiveness of herbal drugs is substantial and they have insignificant side effects than the synthetic antidiabetic drugs. There is growing demand by patients to use the natural products with antidiabetic activity. In recent times there has been improved concern in the plant remedies. Plants grasp certain potentials in the organization of Diabetes mellitus. Isolation and documentation of active ingredients from these plants, preparation of unvarying dose and dosage schedule can play a noteworthy role in improving the hypoglycemic action (Jung et al. 2006).

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