A Review On Herbal Antidiabetic Drugs Edited

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A Review on Polyherbal Formulation for Anti-diabetic activity

Pradeep Suva, Payal Dande

School of Pharmacy & Technology Management, SVKM’s Narsee Monjee Institute of


Management Studies (NMiMS), Babulde, Bank of Tapi River, Mumbai – Agra Road,
Shirpur, Dist. Dhule, Maharashtra 425405
Abstract:

Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose
resulting from defects in insulin production, insulin action, or both. Diabetes mellitus (DM),
both insulin-dependent DM (IDDM) and non-insulin dependent DM (NIDDM) is a common
and serious metabolic disorder throughout the world. The third type of Diabetes which is
most commonly observed is Gestational diabetes. Macro vascular and Micro vascular
complications are observed in diabetes. Micro vascular complications Includes: neuropathy
(nerve damage), nephropathy (kidney disease), vision disorders (e.g. retinopathy, glaucoma,
cataract and corneal disease). Macro vascular complications Includes: Heart disease Stroke &
Peripheral vascular disease (which can lead to ulcers, gangrene and amputation). History
showed that medicinal plants have been used in traditional healing around the world for a
long time to treat diabetes. Among many medications and other alternative medicines, several
herbs have been known to cure and control diabetes; additionally they have no side effects.
The present paper is an attempt to review major herbal anti-diabetic formulations, their
composition and the related beneficial effects of major herbs originating from different parts
of the world. This review focuses on emphasizing the pharmacological effect of the various
herbs that are used in these formulations for treating diabetes and its several complications.
The paper also highlights the therapeutic advantage and merits of these medicinal herbs that
are available as marketed preparations for prevention of diabetes mellitus.

Key Words: Anti-diabetic activity, New & Emerging Therapies, Herbal medicine Traditional
knowledge, Polyherbal Formulation.
1.0 Introduction on Diabetes:

Diabetes, a state of improperly regulated homeostasis of carbohydrate and lipid metabolism is


one of the major health problem in recent time. Traditional Medicines derived from medicinal
plants are used by about 70% of the world’s population. Indians are genetically more
susceptible to diabetes, for which World Health Organization predicts the number of diabetic
persons in India may rise up to 74 million by 2025(1).

Despite the numerous preventative strategies and armouries of medication, the management
of type 2 diabetes remains grossly unsatisfactory. Diabetes is emerging as a pandemic.
Diabetes is predicted to increase by 27% in developed countries and 48% in developing
countries from 1995 to 2025(2). The latest WHO estimate (for the number of people with
diabetes, world-wide, in 2000) is 177 million. This will increase to at least 300 million by
2025 (3). With increasing reliance on multiple patented pharmacological agents to meet targets,
the cost of treatment has also become a real concern.

1.1 Current therapy:

The advance of new classes of glucose-lowering medications to supplement older drugs


(insulin, sulfonylureas, metformin) has certainly widened the palette of available treatments
and possible combinations; however, it has also highlighted the indecision that accompanies
the selection of appropriate therapeutic regimens for the heterogeneous population of patients
with diabetes. With regard to lifestyle alterations, over nutrition and a sedentary lifestyle
(both contributing to obesity) are the major environmental factors that increase the risk of
Type 2 DM. Not surprisingly, exercise and weight loss almost always increase glycemic
levels, as well as other CVD risk factors (e.g., blood pressure, atherogenic lipid profiles). The
benefits of these lifestyle alterations are usually seen rapidly (within weeks to months), and
often before substantial weight loss occurs.

1.2 Pharmacologic Therapy


A major factor in choosing initial therapy or in changing therapy is the level of glycemic
control. When levels of glycemia are high, classes with greater and more rapid glucose-
lowering effectiveness, or potentially earlier initiation of combination therapy, are
recommended. Likewise, when glycemic levels are closer to target goals (e.g., A1C <7.5%),
medications with lower hypoglycemic potential and/or a slower onset of action may be
considered. Since type 2 diabetes mellitus is a progressive disease, the addition of
medications to control worsening glycaemia over time tends to be the rule rather than the
exception. The following sections provide an overview of traditional and newer/emerging
agents used in T2DM (4, 5, 6).

1.2.1 Metformin

The solitary biguanide available in most of the world, metformin lowers glycemia by
reducing hepatic glucose output and increasing insulin sensitivity. While metformin mono
therapy is usually not accompanied by hypoglycemia and has been used securely in patients
with pre diabetic hyperglycemia, concomitant use with other agents (e.g., insulin,
sulfonylureas) may result in hypoglycemic episodes. Although lactic acidosis is rarely
reported, this complication has a potentially fatal outcome (7).

1.2.2 Sulfonylureas

Sulfonylureas lowers the glucose levels by enhancing insulin secretion and appear similar to
metformin in efficacy at lowering A1C levels (1.5% reduction). Metformin, however, is
associated with better long-term maintenance of glycemic targets. The major adverse
consequence related with sulfonylureas is hypoglycemia, with severe episodes (accompanied
by coma or seizures) being infrequent and more common in elderly patients (8, 9).

Various other class of drugs are also used for antidiabetic activity such as: α-Glucosidase
Inhibitors, Thiazolidinediones (TZDs or Glitazones).

1.3 New and Emerging Therapies:

Incretin-Based Therapies: Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl


Peptidase-4 Inhibitors

Incretin hormones, the major ones being glucose-dependent insulinotropic polypeptide (GIP)
and glucagon-like peptide-1 (GLP-1), are involved in the regulation of blood glucose, and to
a lesser extent, insulin and glucagon secretion. Both GLP-1 and GIP are considered glucose
dependent hormones, meaning that they are secreted when glucose levels rise above fasting
levels and that they indirectly stimulate insulin secretion. Normally, these incretin hormones
are released from endocrine cells in the small intestine in response to oral nutrient ingestion
and, by activating G protein–coupled receptors on pancreatic β-cells, they aid in stimulation
of insulin secretion. GLP-1 also reduces the secretion of glucagon, a hormone produced by
the pancreas that stimulates the liver to convert glycogen to glucose (10, 11).

1.3.1 Newer Techniques are as follows: Micro Needles, Needle Free Injection Technology,
Beta cell transplantation, Non-injectable formulations of insulin, Inhaled (nasal).

1.3.2 The mechanism of action of Type 1 and Type 2 Diabetes:

Figure 1: Mechanism of Action


The cost of metformin is 3 to 5-fold higher than that of the cheapest generic sulphonyl ureas.
This spirals to 6-fold higher for repaginate and 30-fold higher for thiazolidinedione’s. (12, 13)

2 Various Herbal Formulations used for diabetes are as follows:

According to the study carried out by World Health Organization (WHO), about 3/4th of the
world population depends upon traditional remedies (mainly herbs) for the health care of its
people. In fact, herbs/plants are the ancient friends of mankind. They not only provided food
and shelter but also helped the humanity to cure different ailments. The herbal medicine are
also sometimes called as, traditional or natural medicine existed in one way or another in
different cultures/civilizations, such as Western, Egyptians, Kampo (Japan), Chinese,
Ayurveda (India), and Greco-Arab or Unani/Tibb (South Asia) (14). Ayurveda is a great Indian
(15)
tradition and have an important role in discovery of new medicines . Various herbal plants
have been reported for their antidiabetic action which is categorized as follows with their
different marketed formulations:

Major formulations used in Ayurveda are based on herbs used as decoctions, infusion,
tinctures and powders. Drug formulation in Ayurveda (As mention in Ayurveda treatise like
Charaka Samhita, Sushruta Samhita) is based on two principles: (a). Use as single drug, and
(b). Use of more than two drugs. When two or more herbs are used in formulation they are
known as polyherbal formulation. Sometimes herbs are combined with mineral preparation.

The concept of polyherbalism is peculiar to Ayurveda although it is difficult to


explain in term of modern parameter. Sarandghar Samhita highlights the concept of
synergism behind polyherbal formulations. Ayurveda has fundamental aspects for drug
formulation. The herbs are selected according to disease other herbs are used to prevent side
effect arising from chief herb. It is evident that there are many herbal formulations of varying
potency since these preparation act by different mechanism, it is theoretically possible that
different combination of these extract will do better job in reducing blood glucose. In the
traditional system of plant medicine it is usual to use plant formulation and combined extract
(16)
of plant are used as a drug of choice rather than individual ones , to get the benefit of
synergism and to find suitable antidiabetic therapy. Here we focuses on individual and
potentials of different polyherbal formulation that have been confirmed by scientific
investigation, which appear to be most effective relatively nontoxic and have substantial
documentation of efficacy.

Carbohydrate
ENZYMES DIGESTIVE

Glucose

ENZYMES

Ocimum
sanctum
Glucose

Insulin

Curcuma Eugenia
longa jambolana
Momordica
charantia

Emblica
officinalis

Figure: Various Herbs showing the target of their action for Antidiabetic activity

2.1Dihar

A polyherbal formulation containing eight different herbs Syzygium cumini,


Momordica charantia, Emblica officinalis, Gymnema sylvestre, Enicostemm, Azadirachta
indiaca, Tinospora cordifolia and Curcuma longa. Literatures revealed that combination of
these eight herbs shows effective Anti-hyperglycemic activity in Strptozotocin (STZ, 45
mg/kg IV single dose) induced type 1 diabetic rats. Treatment with Dihar (100 mg/kg) for 6
weeks produced decrease in STZ induced serum glucose and lipid levels and increases insulin
levels as compared to control. Dihar produced significant decrease in serum creatinine urea
level and lipid peroxidation in diabetic rats. Administration of Dihar to diabetic rats
significantly increased the activity of antioxidant enzyme (17).

2.2Diabet

A polyherbal formulation containing Curcuma longa, Coscinium fenestratum


Strychnos potatorum, Phyllanthus reticulatus. Tamarindus indica, Tribulus terrestris and
containing marketed for diabetes was investigated for its glucose tolerance and antidiabetic
activity in alloxan induced diabetic rats. The glucose tolerance test and hypoglycemic studies
carried out in normal rats at a dose of 500mg/kg. The product showed its effectiveness at a
dose of 500 mg/kg but does not hypoglycemic effect (17).

2.3Diasol
A polyherbal antidiabetic formulation containing plant extracts of Eugenia jambolana,
Foenum graceum, Terminalia chebula, Quercus, infectoria, Cuminum cyminum, Taraxacum,
officinale, Emblica officinalis, Gymnea sylvestre, Phyllanthus nerui and Enicostemma
littorale (Babuji.et al. 2010) Previous investigation showed Diasol produced 63.4 % reduction
of blood glucose level in a dose of 125 and 250 mg/kg b.w i.p and proved to be effective
antidiabetic polyherbal formulation (18).

2.4Dianex

A polyherbal formulation was screened for antidiabetic activity in rats and it has been
reported in literatures that Dianex produce significant hypoglycemic activity in both normal
and diabetic mice. It was administered orally in different doses of 100, 250 and 500 mg/kg
bw up to 6 weeks. Research concluded that the continuous administration of Dianex up to 6
weeks showed it to be effective in long term treatment (19).

2.5Karnim Plus

An indeginous polyherbal formulation containing Momordica charantia, Azadirachta


indica, Picrorrhiza kurroa, Ocimum sanctum and Zinziber officinale was evaluated for
antidiabetic activity and it was found that product showed effectiveness at two dose levels at
200 mg/kg and 400 mg/kg bw for antidiabetic activity (20).

2.6Diasulin

A polyherbal formulation containing Cassia auriculata, Coccinia indica, Curcuma


longa, Emblica officinalis, Gymnema sylvestre, Momordica charantia, Scoparia dulcis,
Syzygium cumini, Tinospora cordifolia, Trigonella foenum graecum Previous Investigation
suggest that controls the blood glucose level by increasing glycolysis and decreasing
gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is
possible, because it regulates the activities of hepatic glucose metabolic enzymes (21).

2.7Diabecon

A polyherbal formulation containing Gymnema sylvestre, Pterocarpus marsupium,


Glycyrrhiza glabra, Casearia esculenta, Syzygium cumini, Asparagus racemosus, Boerhavia,
diffusa, Sphaeranthus indicus, Tinospora cordifolia, Swertia chirata, Tribulus terrestris,
Phyllanthus amarus, Gmelina arborea, Gossypium herbaceum, Berberis aristata, Aloe vera,
Triphala, Commiphora wightii, shilajeet, Momordica charantia, Piper nigrum, Ocimum
sanctum, Abutilon indicum, Curcuma longa, Rumex maritimus is reported to increase
peripheral utilization of glucose, increase hepatic and muscle glucagon contents, promote B
cells repair and regeneration and increase c peptide level. It has antioxidant properties and
protects B cells from oxidative stress. It exerts insulin like action by reducing the glycated
haemoglobin levels, normalizing the micro albumin urea and modulating the lipid profile. It
minimizes long term diabetic complications. Previous Studies also revealed that Diabecon is
a safe drug to prevent complications such as retinopathy in diabetic patients. Diabecon
resolved retinal and vitreal haemorrhages and its subsequent prevention. It also enhanced the
absorption of hard and soft exudates by anti-inflammatory properties Studies concluded that
Diabecon can be used as an adjuvant with conventional treatment in NIDDM and IDDM
patients.

2.8Diabecure

A formulation containing Juglans regia, Berberis vulgaris, Erytherea centaurium


Millefolium, Taraxacum effective in lowering the blood sugar level.

2.9Diabeta

A formulation containing Gymnema sylvestre, Vinca rosea (Periwinkle), Curcuma


longa (Turmeric), Azadirachta indica (Neem), Pterocarpus marsupium (Kino Tree),
Momordica charantia (Bitter Gourd), Syzygiumcumini (Black Plum), Acacia arabica (Black
Babhul), Tinospora cordifolia , Zingiber officinale (Ginger) available in the capsule form is
an anti-diabetic with combination of proven anti-diabetic fortified with potent
immunomodulators, antihyperlipidemics, anti-stress and hepatoprotective of plant origin. The
formulation of Diabeta is based on ancient ayurvedic references, further corroborated through
modern research and clinical trials. Diabeta acts on different sites in differing ways to
effectively control factors and pathways leading to diabetes mellitus. It attacks the various
factors, which precipitate the diabetic condition, and corrects the degenerative complications,
which result because of diabetes. Diabeta is safe and effective in managing Diabetes Mellitus
as a single agent supplement to synthetic anti-diabetic drugs. Diabeta helps overcome
resistance to oral hypoglycemic drugs when used as adjuvant to cases of uncontrolled
diabetes. Diabeta confers a sense of well-being in patients and promotes symptomatic relief
of complaints like weakness giddiness, pain in legs, body ache, polyuria and pruritis (22).

Manufacturers
Brand Name Compositions
Name
Vijaysar (Pterocarpusmarsupium); Gurmar
1. Diabetes Cure
Bliss Ayurveda (Gymnemasylvestre); Karela
(GLUCOGARD)
(Momordicacharantia)
Shelter Pharma GudmarButi (Gymnema Sylvestre), Jambu Seed
2. Diabetone Tablet
Ltd. (Eugenia Jambolana), Karela (Bitter melon)
Meshashringi (Gymnemasylvestre), Pitasara
(Pterocarpusmarsupium),Yashti-madhu
(Glycyrrhizaglabra), Saptarangi
(Caseariaesculenta), Jambu (Eugenia jambolana
Syn. Syzygiumcumini), Shatavari (Asparagus
3. Dianbecon Himalaya
racemosus), Punarnava
(Boerhaaviadiffusa),Mundatika
(Sphaeranthusindicus), Guduchi
(Tinosporacordifolia), Kairata (Swertiachirata
Syn. S.chirayita), Gokshura (Tribulusterrestris)
Gymnema sylvestre, Eugenia jambolana,
Krishna Herbals, Momordica charantia Azadirachta indica, Cassia
4. Dianex
Ahmedabad auriculata, Aegle marmelose, Withania
somnifera and Curcuma longa
Karela (Bitter melon), GudmarButi
The varma
4. Dybogen (GymnemaSylvestre), Jambu Seed (Eugenia
pharmcy
Jambolana)
5. Dyboss anti-diabetic Laghugokshur (TribulusTerristris), Karvellak
Morpheme Herbals
caps (Bitter Gourd)
Momordica, Gymnema, Salacia,
6. Diabeta plus Morpheme Herbals
Pterocarpusmarsupium
7. Diasulin. Goodwill herbal
Allium sativum
products
8. Diaveda capsule. Indus Valley Methika (Trigonellafoenum-graecum),
Ayurvedic Centre Madhunashini (Gymnemasylvestre) Gokshura
(Tribulusterrestris), Guduchi
(Tinosporacordifolia), Jambu
(Syzygiumcumuni), Kiratatikta (Swertiachirata),
Nisha (Curcuma longa), Nimba
(Azadirachtaindica), Triphala
(Embicaofficinalis), Terminaliabelerica &
Terminaliachebula), Trikadu (Piper nigrum,
Piper longum&Zingiberofficinalis)
9. Dia-care herbal Admark Herbals
Belpatra, Bivala, Gudmar, Jambu and Karela
powder Limited
Saptrangi (Salaciaoblonga), Gurmaar
(Gymnemasylvestrae), Karela
10. Dia Beta Plus Planet Ayurveda
Momordicacharantia)
Vizaysaar (Pterocarpusmarsupium)
Amalaki Ghana, Belpatra, Bivala, Gudmar,
11. Diabohills Herbal Hills
Jambu and Karela
Emblicaofficinalis, Aeglemarmelos,
Vedic Kaya
12. Dease Tinosporacordifolia, Azadirachtai ndica, Acacia
Place: New delhi
arbica, Momordiacharantia, Gymnemasylvestre.
Pongamia Glabra, Gymnema sylvestre,Syzygium
cumini,Tinospora cordifolia, Emblica officinalis,
Ayurvedic Momordica charantia, Caseriana esculenta,
13. Diabkill Capsules Research Trigonella foenumgraecum, Curcuma longa,
foundation Silajit Shuddha, Vanga Bhasma, Abhraka
Bhasma, Kanta loha Bhasma, Citrullus
colocynthis, Cassia auriculata
Embilica Officinalis, Aegle Marmelos, Eclipta
Alba,
TinosporaCardifolia, Gymnema Sylvestre,
14. Diab Care Tablets Sanjivani Health Syzygiul Cumini, Momordica Charantia,
Enicastemma Lottorala,
Azadiracta Indica, Curcuma Longa, Swerita
Chirayata
15. Diabet Guard Good Care Karela, Khadir, Haldi, Amla, Biyoysar, Tejpatta,
Sudh silajeet, Neem patti, Gullar patti, Kutki,
Chitrak, Gurmar, Jamun Guthali, Giloy, Methi,
Tribanga Bhasma
HERBAJULES - Musk melon seeds, Momordicacharantia,
16. DIAMELON PLUS Herbal Syzigiumcumini, Trigonellafoenum,
Supplements Azadirachtaindica,
HERBALWAYS
Neem, Ashwagandh, Stawar, Gokhru, Safed
17. DIABODYTE DIETS, Place:
musli, Kaunch beej
Jalandhar
Pterocarpus mersupium, Momordica charantia,
Varuna Biocell Pvt.
18. Episulin Eugenia jambolana, Cinnamom tamala
Ltd.
Trigonella foenum, Picrorrhiza kurroa.
19. Glucocare Guggul, Gymnena, Indian tinospora,
Himalaya
phyllanthusamarus, holy basil
20. Glucolib Virage Sante Ginseng, green tea
21. Gymnema Ayurvedic series Gymnema Extract
Isha Agro
22. Herbal Hills Jambu Jambubeej extract
Developers
Krishna herbal
23. Kumari-SAAR Aloe Vera Juice
company
Dry Karela (Momordicacharantia), Neempatra
Unijules Life (Azadirachtaindica), Tulsi (Ocimum sanctum),
24. Karnim Capsule
Science Ltd. Kutki (Picrorhizakurroa),Shuddhaguggul
Commiphoramukul, Sonth (Zingiberofficinale)
25. Karela Morpheme Herbals Karela Extract
Emblicaofficinalis, Aeglemarmelos,
Kangrd Hills Care
26. Madhumar capsule Tinosporacordifolia, Azadirachtai ndica, Acacia
& Cure Products
arbica, Momordiacharantia, Gymnemasylvestre.
Momordicacharantia, Syzigiumcumini,
Trigonellafoenum, Azadirachtaindica,
27. Madhuhari powder Baidhyanath
Emblicaofficinalis, Curcuma longa,
Gymnemasylvestre, Pterocarpusmarsupium.
Tinosporacordifolia, Azadirachtaindica,
Gymnemasylvestre, Withaniasomnifera,
28. Madhunasinivati Divya Pharmacy Trubululsterrestris, Terminaliachebula,
Terminaliabelerica, Adhatodavasica,
Picrorhizakurroa
29. Madhumukti Pruthvi Ayurvedic Gymnema sylvestre,Syzygium cumini,Tinospora
cordifolia, Emblica officinalis, Momordica
charantia, Caseriana esculenta, Trigonella
foenumgraecum, Curcuma longa, Silajit
Pharmaceutical
Shuddha, Vanga Bhasma, Abhraka Bhasma,
Place: Karnataka
Kanta loha Bhasma, Swarna maksika Bhasma,
Bhavana Kumari Swarasa, Nimba Swarasa,
Bilva Swarasa, Pramehahar Kwatha.
Momordicacharantia, Syzigiumcumini,
Trigonellafoenum, Azadirachtaindica,
30. Madhuhari Churna Shivayu Herbals
Emblicaofficinalis, Curcuma longa,
Gymnemasylvestre, Pterocarpusmarsupium.
31. Optimum Diabetics
Plant Med. Lab
32. Sharang Dyab-Tea Dyab Tea Gudmar and Vijayasar extracts
Pvt. Ltd
Shriji Herbal
33. Spenai Haritaki, Gudumar, Mulethi, Indrajav
Produts
Hakeem Chichi Laghugokshur (TribulusTerristris), Karvellak
34. Ziabetol
Pharmacy (Bitter Gourd)

a) Abelmoschus moschatus (Malvaceae): It is an aromatic medicinal plant, which is native


to India. Myricelin, an active principle of A. moschatus, improves insulin sensitivity
through increased post-receptor insulin signalling mediated by enhancements is
associated PI3-kinase and GLUT 4 activity in muscles of obese Zucker rats(23).

Fig: Abelmoschus moschatus

b) Acacia Arabica (Mimosaceae): It is found all over India. The plant extract acts as an
antidiabetic agent by acting as Secretagogues to release insulin. It induces hypoglycemia
in control rats but not in alloxanized animals. Powdered seeds of A. arabica when
administered (2, 3 and 4 g/kg body weight) to normal rabbits, induces hypoglycemic
effect by initiating release of insulin from pancreatic beta cells (24).

Figure: Acacia Arabica

c) Achyranthes aspera L (Amaranthaceae): It is distributed throughout the tropical world.


Oral administration of A. aspera powder produces a significant dose-related
hypoglycemic effect in normal as well as in diabetic rabbits. The water and methanol
extracts also decreases blood glucose levels in normal and alloxan diabetic rabbits. The
acute toxicity study in rabbits does not reveal any adverse or side effects of this folk
medicine at dosages up to 8 g/kg orally (25).

Figure: Achyranthes aspera


d) Aegle marmelose (Rutaceae): A species of tree native to India, it is present throughout
Southeast Asia as a naturalized species. A significant decrease in liver
glycogen of diabetic rats is reversed to almost the normal level by the leaf extract
and it also decreases the blood urea and serum cholesterol. A similar effect is seen with
insulin treatment and the results indicate that the active principle in A. marmelos leaf
extract has similar hypoglycemic activity to insulin treatment (26).

Figure: Aegle marmelose

e) Aloe Vera (Family: Liliaceae), Aloe, a popular houseplant, has a long history as a
multipurpose folk remedy. The plant can be separated into two basic products: gel and
latex. Aloe Vera gel is the leaf pulp or mucilage, aloe latex, commonly referred to as
“aloe juice,” is a bitter yellow exudate from the pericyclic tubules just beneath the outer
skin of the leaves. Extracts of aloe gum effectively increases glucose tolerance in both
(27)
normal and diabetic rats . Treatment of chronic but no single dose of exudates of Aloe
barbadensis leaves showed hypoglycemic effect in alloxanized diabetic rats. Single as
well as chronic doses of bitter principle of the same plant also showed hypoglycemic
effect in diabetic rats. This action of Aloe Vera and its bitter principle is through
(28)
stimulation of synthesis and/or release of insulin from pancreatic beta cells . A. Vera
leaf pulp and gel extracts were ineffective in lowering the blood sugar level of no diabetic
rats, but the leaf pulp extract showed hypoglycemic activity in diabetic rats (29).
Figure: Aloe Vera

f) Anthemis nobilis Linn. (Family: Compositae): Anthemis nobilis Linn.is a 3 hydroxy‐3‐


methylglutaric acid (HMG) containing flavonoids, glucoside hamaemeloside which has
been shown to have in vivo hypoglycaemic activity comparable to that of free HMG (30).
In humans, this plant is among twelve herbs most commonly used to treat diabetes in
Saudi Arabia (31). In Alloxan treated rabbits and mice, it has been shown that the
aqueous extract of the plant produced an initial hyperglycaemia which was followed by
hypoglycaemia (32).

Figure: Anthemis nobilis

g) Artemisia pallens (Family: Compositae): Oral administration of an extract of the aerial


parts of Artemisia pallens. Produced a dose‐dependent reduction in glycaemia in Alloxan
induced diabetic rats. In fasted healthy rats, the extract caused moderate hypoglycaemia at
a higher dose. Only the methanol extract was active whereas the water extract was
inactive (33).
Figure: Artemisia pallens

h) Asteracantha longifolia (Family: Acanthaceae): Oral administration of the extract of


Asteracantha longifolia. (20 g/kg of starting material) can significantly improve glucose
tolerance in healthy human subjects and diabetic patients (34).

Figure: Asteracantha longifolia


i) Azadirachta indica (Family: Meliaceae): An Azadirachta indica leaf extract was found
to have no action on peripheral utilization of glucose or on hepaticglycogen in healthy
and streptozotocin‐induced diabetic rabbits. The reduction in peripheral utilization of
glucose and glycogenolytic effect due to epinephrine was blocked by the A. indica leaf
extract, almost completely in diabetic rabbits and to a certain extent in healthy animals.
More recently, it has been demonstrated that in an in vitro rat pancreas preparation, A.
indica leaf extract significantly blocked the inhibitory effect of serotonin on insulin
secretion mediated by glucose (35, 36).

Figure: Azadirachta indica


j) Bombax ceiba (Family: Bombacaceae): In Sprague‐Dawley rats, a dose of 500 mg/kg of
Shamimin (a Cflavonol glucoside from Bombax ceiba) produced a significant reduction
in glycaemia (37).

Figure: Bombax ceiba

k) Brassica juncea (Family: Brassicaceae), this study demonstrated the effect of Brassica
juncea (Leaf Mustard) on carbohydrate metabolism in rats. It showed significant
hypoglycaemic action. There was increased activity of glycogen synthetase, and a
decrease in glycogenolysis and gluconeogenesis demonstrated by a decreased activity of
glycogen phosphorylase and gluconeogenic enzymes (38).

Figure: Brassica juncea

l) Caesalpinia bonducella (Family: Cesalpinaceae), In healthy rats, both the aqueous and
50 % ethanolic extracts of Caesalpinia bonducella seeds exhibited hypoglycaemic
activity as early as 4 h after administration at a lower dose of 100 mg/kg. The
hypoglycaemia produced by the aqueous extract was of prolonged duration as compared
to the ethanolic extract. In diabetic rats, both extracts produced marked anti-
hyperglycaemic effects from 5th day onwards (39).

Figure: Caesalpinia bonducella

m) Catharanthus roseus (Family: Apocynaceae): Oral administration of the aqueous


fraction of an alcoholic extract of leaves of Catharanthus roseus leads to marked
lowering of glycaemia in normal and streptozotocin‐induced diabetic rats. This effect was
comparable with that of tolbutamide (40).

Figure: Catharanthus roseus

n) Cinnamomum (Lauraceae), is also known as Indian Cassia and the leaves are
commonly called as bay leaves. The genus Cinnamomum is represented by about 350
species worldwide. Natural habitat is in the tropical and sub-tropical Himalayas at
altitudes of 900-2500 m. C. tamala had a beneficial effect on the hyperlipidemia induced
by STZ. Ethanolic extract of C. tamala exhibit significant antiyperglycemic activities in
STZ-induced rats (41).
Figure: Cinnamomum

o) Coriandrum sativum (Apiaceae): An annual herb native to southern Europe and


North Africa to south-western Asia. Coriander seed extract (200 mg/kg) significantly
increases the activity of the beta cells in comparison with the diabetic control rats and
decreases serum glucose in Streptozotocin-induced diabetic rats and releases insulin
from the beta cells of the pancreas (42). The extract shows anti-hyperglycemic,
insulin-releasing and insulin-like activity (43).

Figure: Coriandrum sativum

p) Curcuma longa (Family: Zingeberaceae), commonly known as Haldi in Hindi has been
used as spice and colouring agent. Although C. longa has been investigated for its various
medicinal properties, detailed studies on its anti-diabetic is also carried out. By attention
to most good effective roles of this plant, therefore the aim of present study is to
determine the protective effect of turmeric (Curcumalonga Linn.) powder on early
diabetic nephropathy in rats.(44, 45)
Figure: Curcuma longa
q) Emblica officinalis (Family: Euphorbiaceae), Different solvent extracts of E.
officinalis acts as α-amylase and α-glucosidase inhibitor. Significant antiglycation
activity also confirms the therapeutic potential of these extracts against diabetes.
Methanol extracts significantly inhibits the oxidation of LDL under in vitro conditions (46).

Figure: Emblica officinalis

r) Eugenia Jambolana (Family: Myrtaceae), popularly known as Jamun, has been


indicated in Ayurveda for use in diabetes mellitus. In India decoction of kernels of
Eugenia jambolana is used as household remedy for diabetes. As per claims of its anti-
diabetic effects in traditional medicine Eugenia Jambolana has been reported to have
hypoglycaemic effects both in pre-clinical and clinical studies (47).

Figure: Eugenia Jambolana

s) Gymnema sylvestre (Family: Asclepiadaceae): is used as a traditional antidiabetic and


hypolipidemic agent in past and present culture. It is distributed throughout India. The
leaves are known for its antidiabetic activity which is rich in phytochemicals such as
alkaloids, flavonoids, saponins, carbohydrates, and phenols with highest concentration of
saponins being 5.5%. It helps the pancreas with insulin production in type 2 diabetes and
increases the sensitivity to insulin in type 1 diabetics. Reports showed the ability of
gymnemic acids to delay the glucose absorption in the blood due to the atomic
arrangement of gymnemic acid molecules which is similar to that of glucose molecules.
These molecules fill the receptor locations on the taste buds thereby preventing its
activation by sugar molecules present in the food, thereby curbing the sugar craving.
Similarly Gymnemic acid molecules fill the receptor location in the absorptive external
layers of the intestine thereby preventing the sugar molecules absorption by the intestine,
which results in low blood sugar level (48, 49).

Figure: Gymnema sylvestre


t) Momordica charantia L. (Family: Cucurbitaceae), M. charantia (bitter melon) is
commonly known as vegetable insulin. An oral sucrose tolerance test reveals that
administration of aqueous extract (AE), methanol fraction (MF) or methanol insoluble
fraction (MIF) each significantly suppresses plasma glucose levels at 30 min as compared
with control. In addition, the plasma insulin level at 30 min also lowers after MF
administration than the control in the oral sucrose tolerance test, these results
demonstrates that bitter melon suppresses postprandial hyperglycemia by inhibition of α-
glucosidase activity (50).

Figure: Momordica charantia

u) Ocimum sanctum (holy basil), It is commonly known as Tulsi. Since ancient times, this
plant is known for its medicinal properties. The aqueous extract of leaves of Ocimum
sanctum showed the significant reduction in blood sugar level in both normal and alloxan
induced diabetic rats. Significant reduction in fasting blood glucose, uronic acid, total
amino acid, total cholesterol, triglyceride and total lipid indicated the hypoglycemic and
hypolipidemic effects of tulsi in diabetic rats. Oral administration of plant extract (200
mg/kg) for 30 days led to decrease in the plasma glucose level by approximately 9.06 and
26.4% on 15 and 30 days of the experiment respectively. Renal glycogen content
increased 10 fold while skeletal muscle and hepatic glycogen levels decreased by 68 and
75% respectively in diabetic rats as compared to control. This plant also showed
antiasthemitic, antistress, antibacterial, antifungal, antiviral, antitumor, gastric antiulcer
activity, antioxidant, antimutagenic and immunostimulant activities (51, 52, 53).
Figure: Ocimum sanctum

v) Pterocarpus marsupium (Family: Leguminoceae) is widely used in ‘Ayurveda’ as


‘Rasayana’ for the management of various metabolic disorders including hyperglycemia.
Treatment of diabetic rats with Pterocarpus marsupium methanol extract (PMMtE, 300
mg/kg b.w. /day) for 7 and 14 days showed normalization of streptozotocin-distressed
serum glucose (54).
w) Syzygium cumini (Myrtaceae), is widely used traditional system of medicine to treat
diabetes in India. A compound, mycaminose is isolated from SC seed extract, for
antidiabetic activity. Study shows anti- diabetic effect of ethyl acetate and methanolic
extracts of SC seed and isolated compound mycaminose, against streptozotocin-induced
diabetic rats. The continuous treatment of the extracts of SC for a period of 15 days
produced a significant decrease in the blood sugar levels of diabetic rats (55).
x) Terminalia chebula (Family: Combretaceae), has an esteemed origin in Indian
mythology; its fruits are used to treat many diseases such as digestive, diabetes. The
extract has been shown to possess glucose lowering activity and to improve insulin
sensitivity in animal models of type 2 diabetes mellitus (56, 57).

Figure: Terminalia chebula


y) Tinospora cordifolia (Family: Menispermaceae), commonly known as Guduchi, an
herbaceous vine indigenous to the tropical areas of India, Myanmar and Sri Lanka. Oral
administration of an aqueous T. cordifolia root extract to Alloxan diabetic rats causes a
significant reduction in blood glucose and brain lipids. The aqueous extract at a dose of
400 mg/kg could elicit significant antihyperglycemic effect in different animal models, its
effect is equivalent to only one unit/kg of insulin (58, 59).

Family: Tinospora cordifolia

z) Tribulus terrestris: is used in the Arabic folk medicine to treat various diseases. Tribulus
terrestris benefits people against the risk of diabetes, as its extracts significantly decrease
fasting glucose level in diabetic rats. Researchers found that the protective effect of
Tribulus terrestris on STZ-induced diabetic rats may be mediated by inhibiting oxidative
stress.
aa) Trigonella foenum graecum (Family: Papilionaceae), Used both as an herb (the leaves)
and as a spice (the seed) and cultivated worldwide as a semi-arid crop. Oral
administration of 2 and 8 g/kg of plant extract produces dose dependent decrease in the
blood glucose levels in both normal as well as diabetic rats. Administration of fenugreek
seeds improves glucose metabolism and normalizes creatinine kinase activity in heart,
skeletal muscle and liver of diabetic rats. It also reduces hepatic and renal glucose-6-
phosphalase and fructose -1, 6-biphosphatase activity.

Figure: Trigonella foenum graecum


bb)Withania somnifera (Solanaceae), is an important medicinal plant, which is used in
traditional medicine to cure many diseases. Flavonoids were determined in the extracts of
W. somnifera root and leaf. Its leaves are used in Ayurvedic and Unani systems for
(60)
treatment of tumors and tubercular glands . Hypoglycaemic activity of Trasina (an
ayurvedic formulation) consisting of W. somnifera as one of the important constituents
has been established beyond doubt and this activity may be due to its antioxidant
(61)
properties . Flavonoids are commonly found in all plants and also possess
hypoglycemic and antidiabetic activities, hence it is useful for antidiabetic activity (62).

Figure: Withania somnifera

3.0 Conclusion:
Phyto-therapy for diabetes has been followed all over the World successfully. Herbs are used
to manage Type 1 and Type II diabetes and their complications. The plants mentioned above
have been considered for their possible hypoglycemic activity. Scientific validation of several
Indian plant species has proved the efficacy of the botanicals in reducing the blood sugar
level. However, there are numerous other plants still await scientific inquiry, which have
mentioned in the indigenous systems of medicine for health care all over the world. However,
the interest in herbal drug research continues with an expectation that someday or the other,
we would be able to bring a safer and more effective compound with all the desired
parameters of a drug that could replace the synthetic medicines.

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