**2.2 Diabetes mellitus**

### **2.2.1 What is Diabetes?**

The word "diabetes" (a Greek word that means "to pass through") was first used by Aretaeous of Capadocia in the 2nd century AD to describe a condition that is characterized by excess of sugar in blood and urine, hunger and thirst (MacFrlance et al.,1997) and the adjective "mellitus" (a latin-greek word that means "honey") was introduced by the English physician John Rollo so as to distinguish the conditions from other polyuric diseases, in which glycosuria does not occur (Rollo 1797). People suffering from diabetes are not able to produce or properly use insulin in the body and therefore chronic hyperglycemia occurs. In addition, the diabetic individual is prone to late onset complications (Fujisawa et al., 2004), such as retinopathy, neuropathy and vascular diseases, that are largely responsible for the morbidity and mortality observed in diabetic patients.

origin have been found to be potential sources of novel molecules for the treatment of

Considering the rate at which the vegetation is getting depleted in this part of the world, therefore it is needed to document the precious knowledge of these plants and to search for more plants with antidiabetic potential. The search for anti-diabetic agents has been focused on plants because of their ready availability, effectiveness, affordability and probably due to low side effects (Marles and Farnsworth, 1995). Ethnobotanical study has been the method often used to search for locally important plant species with low side effects especially for the discovery of crude drugs (Farnsworth, 1994). The present study therefore is a documentation of plants and plant parts used for the management of diabetes mellitus by

**Diagnosis methods Respondent (%)**

40 60

100 0

80 20

diabetes (Farnsworth, 1994; Marles and Farnsworth, 1995).

Signs and symptoms Loss of body weight Body weakness Excessive urination Presence of sugar in urine Excessive thirsty

**Duration of treatment** Short duration Long duration

**Efficacy of plant treatment on patients** Disappearance of sugar in urine 100 Reduction in body weakness 100 Normal body weight 100 Reduction in frequency of urination

**Traditional healers claim of no adverse effect after treatment** Yes No

**Traditional healers claim of total cure after treatment** Yes No

morbidity and mortality observed in diabetic patients.

Table 1. Diagnosis methods of diabetes mellitus by the herbalists using herbal preparation

The word "diabetes" (a Greek word that means "to pass through") was first used by Aretaeous of Capadocia in the 2nd century AD to describe a condition that is characterized by excess of sugar in blood and urine, hunger and thirst (MacFrlance et al.,1997) and the adjective "mellitus" (a latin-greek word that means "honey") was introduced by the English physician John Rollo so as to distinguish the conditions from other polyuric diseases, in which glycosuria does not occur (Rollo 1797). People suffering from diabetes are not able to produce or properly use insulin in the body and therefore chronic hyperglycemia occurs. In addition, the diabetic individual is prone to late onset complications (Fujisawa et al., 2004), such as retinopathy, neuropathy and vascular diseases, that are largely responsible for the

traditional healers of the area (Table 1).

**2.2 Diabetes mellitus 2.2.1 What is Diabetes?**  Diabetes mellitus is a chronic metabolic disorder characterized by widespread complications. It is the world's largest endocrine disease associated with increased morbidity and mortality rates (Ghosh and Surawanshi, 2001). The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs (Lyra *et al*., 2006). Liver involvement is one of the leading causes of death in diabetes mellitus. The mortality rate from the hepatic affection is greater than that from the cardiovascular complications. The spectrum of liver implication in diabetes ranges from non-alcoholic fatty liver disease to cirrhosis and eventually hepato-cellular carcinoma (Keith *et al*., 2004). Liver, an insulin-dependent organ, plays a pivotal role in glucose and lipid homeostasis. It participates in the uptake, oxidation and metabolic conversion of free fatty acids and in the synthesis of cholesterol, phospholipids and triglycerides.

Several mechanisms are implicated in the pathogenesis of the functional and morphological alterations of the liver of diabetic patients (Brixova, 1981; Moller, 2001). There are two main types of diabetes, namely type I and type II (World Health Organization. Definition, Diagnosis and Classification of Diabetes mellitus and its omplications. Part 1: Diagnosis and Classification of Diabetes Mellitus (Department of Non communicable Disease Surveillance, Geneva, 1999)). Type I Diabetes, that is called insulin-dependent diabetes mellitus (IDDM) or juvenile onset diabetes develops when the body's immune system destroys pancreatic βells, the only cells in the body that produce the hormone insulin that regulates blood glucose. This type of diabetes usually strikes children and adults and the need for insulin administration is determinant for survival. Type I diabetes accounts for 5% to 10% of all diagnosed cases of diabetes and the risk factors may be autoimmune, genetic, or environmental.

On the other hand, type II diabetes, also called non–insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes, accounts for about 90% to 95% of all diagnosed cases of diabetes. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly and as the need for insulin rises; the pancreas gradually loses its ability to produce it. This type of diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. It must be noted thought that in the last decay type II diabetes in children and adolescents is being diagnosed more frequently (Fagot-Gampagna & Narayan 2001). In the case of the IDDM, insulin is of crucial importance for the survival of the patients. On the other hand, in the case of NIDDM the treatment includes medicines, diets and physical training.

### **2.2.2 Ant diabetic medicines: Important medicinal plants used in diabetes treatment; important active**

### **2.2.2.1 Compounds involved in diabetes mellitus treatment**

Many kinds of antidiabetic medicines have been developed for the patients and most of them are chemical or biochemical agents aiming at controlling or/and lowering blood glucose to a normal level. Despite the impressive advances in health sciences and medical care, there are many patients who are using alternative therapies alone or complementary to the prescribed medication. Traditional plant remedies or herbal formulations exist from ancient times and are still widely used, despite all the controversy concerning their efficacy and safety (Huxtable 1990; Fugh-Berman 2000), to treat hypoglycemic and hyperglycemic conditions all over the world.

It must be noted that many ethno-botanical surveys on medicinal plants used by the local population have been performed in different parts of the world and there is a considerable number of plants described as antidiabetic. In addition a variety of compounds have been isolated (alkaloids, glycosides, terpenes, flavonoids, etc) but further studies need to be done so as these 'leads' to develop into clinically useful medicines. To date, met form in (a biguanide) is the only drug approved for treatment of type II diabetes mellitus. It is a derivative of an active natural product, galegine, isolated from the plant Galega officinalis L. (Witters 2001). The followinf table illustrate some of these plant involved in diabetes mellitus treatment


Table 2. Important medicinal Plants used in Diabetes treatment.

It must be noted that many ethno-botanical surveys on medicinal plants used by the local population have been performed in different parts of the world and there is a considerable number of plants described as antidiabetic. In addition a variety of compounds have been isolated (alkaloids, glycosides, terpenes, flavonoids, etc) but further studies need to be done so as these 'leads' to develop into clinically useful medicines. To date, met form in (a biguanide) is the only drug approved for treatment of type II diabetes mellitus. It is a derivative of an active natural product, galegine, isolated from the plant Galega officinalis L. (Witters 2001). The followinf table illustrate some of these plant involved in diabetes

**constituent Part Used Folk Medical Uses** 

hypoglycemic action decrease

concentrations myricetin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats with

caused significant lowering of blood sugar and reduction in

the plasma glucose

deficient insulin

serum lipids

complications

levels

hypoglycemic effect

damaged pancreas.

lowered blood glucose levels

lowered the plasma glucose

similar hypoglycemic activity to that of insulin treatment Treatment with the leaf extract showed improved functional state of pancreatic β cells. The results indicate the potential hypoglycemic effect of the leaf extract, possibly involved in processes for the regeneration of

levels.

dried powder of root and leaves

powdered whole plant

powdered whole plant

water and butanolic extracts

**macrophylla Cornaceae** prevent and treat diabetic

mellitus treatment

**Scientific** 

**Abelmoschus** 

**Azadirachta** 

**Cornus** 

**Achyranthes** 

**Achyrocline** 

**Acosmium panamense** 

**Aegle** 

**indica Meliaceae** 

**aspera L. Amaranthaceae** 

**satureioides Asteraceae** achyrofuran

**Fabaceae** 

**marmelose Rutaceae** leaf extract

Table 2. Important medicinal Plants used in Diabetes treatment.

**name Family Active** 

**moschatus Malvaceae** myricetin aerial part



alkaloids

**constituent Part Used Folk Medical Uses** 

specific inhibitors of alpha-L fucosidase with no significant inhibitory activity towards other

Arecoline have hypoglycemic activity in animal model of

hypotriglyceridemic, anti-lipid

blood glucose-lowering effect in normal and diabetic rats

hypoglycemic effects that was demonstrated by a per os glucose tolerance test in rats after their per os administration

inhibited the differentiation of naive helper T cells (Th0) into Th1 cells but enhanced their

type II helper T (Th2) cells using an in vitro T cell differentiation

Restore the disordered lipid metabolism of alloxan-diabetic

altered glucose tolerance in alloxan-induced diabetic rats,

uptake in skeletal muscle and significantly inhibited glycogenolysis in the liver.

might contribute to the relief of

the long-term diabetic complications

may be beneficial in the prevention of diabetes mellitus

serious adverse effects

improve serum lipid levels in type II diabetic subjects without

enhanced glucose

glycosidases

diabetes upon s.c. administration

ethanolic extract has hypoglycemic,

peroxidative and antiatherogenic properties in STZ-

diabetic rats.

transition into

assay

rats

pod extract

extract

extract

Butanol extract of whole plant

roots

ethanol extract of root bark

soluble fiber extracted

I, II, III and IV roots

3-beta-Dglucopyranosylo xy-1-hydroxy-6(E)-tetradecene-8,10,12-triyne

derivatives of trihydroxyoctade cadienoic acid

ellagic acid and 2'- (2,3,6 trihydroxy-4 carboxyphenyl) ellagic aci

3-O-gallate

a-tocopherol, ascorbic acid and maltodextrin

Table 2. Important medicinal Plants used in Diabetes treatment.( continuation)

**Scientific** 

**Angylocalyx** 

**Averrhoa** 

**Bauhinia** 

**Beta vulgaris L.** 

**Bumelia** 

**Caesalpinia** 

**Camellia** 

**Bidens pilosa Asteraceae** 

**Bryonia alba L. Curcubiaceae** 

**ferrea Mart Leguminosae** 

**Cassia tora Fabaceae** 

**name Family Active** 

**pynaertii Leguminosae** sugar-mimic

**bilimbi L. Oxalidaceae** ethanolic

**forficata L. Leguminosae** kaempfer itr in n-butanol

**var. cicla Chenopodiaceae** Betavulgaroside

**sartorum Sapotaceae** bassic acid

**sinensis Theaceae** epigallocatechin-

**Areca catechu** arecolin



hydrocortin

**constituent Part Used Folk Medical Uses** 

normal rats.

mediated

type II diabetes

a reduction of

sugar levels

antidiabetic Properties

hypoglycemic and antihyperlipidemic effects

extrac

Water soluble extracts the leaves

acetone extract of the seed hulls

**officinalis L. Leguminosae** Metformin Treat symptoms now ascribed to

Hydnocarpin, Luteolin, And isohydnocarpin

Table 2. Important medicinal Plants used in Diabetes treatment. (continuation)

The mentioned compound also effectively lowered the blood sugar levels in glucose fed

antihyperglycemic effect of cryptolepine leaded to a significant decline in plasma insulin concentration, associated

with evidence of an enhancement in insulin

glucose disposal. Finally, cryptolepine increased glucose uptake by 3T3-L1 cells.

normal and alloxan diabetic rabbits produced significant hypoglycemic effects and the hypoglycemic effects were compared to those of to butamide (Iwu et al., 1998)

Isoorientin exhibited significant

coutareagenin, one of the active substances contained in the Hintonia latiflora bark, produces

the diabetic elevated blood

the presence of antioxidant molecules along with their enzyme inhibitory activities in

the acetone extract of Hydnocarpus wightiana seed hulls may be responsible for the

Gymnemic acids II and III showed potent inhibitory activity on glucose uptake.

**Scientific** 

**Cryptolepis** 

**Dioscorea** 

**Galega** 

**Gentiana** 

**Gymnema** 

**Hintonia** 

**Hydnocarpus** 

**wightiana Arcariaceae** 

**name Family Active** 

**sanguinolenta Asclepiadaceae** cryptolepine

**olivieri Griseb Gentianaceae** isoorientin

**sylvestre Asclepiadaceae** gymnemic acid I

**latiflora Rubiaceae** coutaraegenin

**dumetorum Dioscoreaceae** dioscoretine methanol

**Croton cajucara Euphorbiaceae** trans-


Fig. 1. Some important active compound involved in diabetes mellitus treatment.

O

HO

O

OH

kaempferitrin

HO

O

OH

HO

O

O

HO

HO

O

ellagic acid

O

achyrophuran

HO

O

O

H OH

andrographolide

OH

OH OH <sup>O</sup> OH

12,13,16-trihydroxy-9Z,14E-octadecadienoic acid

OH

OH

O OH

HO O OH

HO

HO

HO

O

OH

O

HO

HO

OH

myricetin

OH

OH

OH

OH O

HO O

S S

O

HO HO

OH

O

HO

HO

HOOC O H

COOH

HOOC HO

O

O H

allic ine

mangiferin O OH

O O

OH

OH

OH

OH

OH

O O

betavulgaroside I

bassic acid

Fig. 1. Some important active compound involved in diabetes mellitus treatment.

<sup>H</sup> COOH HO

O

HO OH

OH OH

O

Fig. 1. Some important active compound involved in diabetes mellitus treatment. (continuation)

perilloside D:1,4-cis

Fig. 1. Some important active compound involved in diabetes mellitus treatment. (continuation)

OH OH

O

OH H

> <sup>O</sup> HOHO <sup>H</sup> O

> > myrciaphenon B

HO

1 4

O

OH

OH

HO

HO HO

OH

HO

HO

O

OH

O

HO

OH

OH

O

O

4-hydroxybenzoic acid

OH

OH O

O

O OH

O

isohydnocarpin

OH

O O

OH O

myrciacitrin II

O

O

OH

OH

OH

O

HO

O O

hydnocarpin luteolin

O O

OH O

myrciacitrin I

O

O

OH

paeoniflorin

HO HO

O

O

OH

OH O

O O

OH

OH O

O

OH O

Fig. 1. Some important active compound involved in diabetes mellitus treatment.

perilloside C:1,4-trans perilloside D:1,4-cis

O OH

HO

OH

O

O

OH H

<sup>O</sup> HOHO <sup>H</sup> OH

> HO HO

(continuation)

OH

myrciaphenon A

OH

OH

OH

HO

OH
